This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
The COVID-19 pandemic was characterized by the emergence and succession of SARSCoV-2 variants abl... more The COVID-19 pandemic was characterized by the emergence and succession of SARSCoV-2 variants able to evade the antibody response induced by natural infection and vaccination.To evaluate the IgG reactivity and neutralizing capacity of the serum of individuals vaccinated with Sputnik V (105 volunteers vaccinated) against different viral variants. IgG reactivity to the Spike protein (S) was evaluated by ELISA. A plaque reduction neutralization test was performed using different viral variant isolates. At 42 days post-vaccination, the frequency of recognition and reactivity to the S protein of the Omicron variant was lower compared to that of the other variants. In general, a higher average neutralization titer was seen against the ancestral variant compared to the variants, especially Omicron. However, some sera exhibited a higher neutralization titer to the Gamma variant compared to the ancestral variant, suggesting unapparent exposure during the clinical trial. Antibodies induced by Sputnik V can recognize, persist, and neutralize SARS-CoV-2 variants, with Omicron being the one that best evades this response. These results represent a unique report on the humoral response induced by a globally lesser-studied vaccine in terms of efficacy and immune escape, offering insights into developing vaccines targeting unknown coronaviruses.
There have been few changes over the last 50 years in the treatment of Systemic lupus erythematos... more There have been few changes over the last 50 years in the treatment of Systemic lupus erythematosus (SLE), using non-specific anti-inflammatory agents such as: non-steroidal anti-inflammatory drugs along with the immune cell modulating agent hydroxychloroquine for mild disease, and broad spectrum immunosuppressants plus anti-inflammatories such as corticosteroids, azathioprine, cyclophosphamide, or mycophenolate during flares or severe disease with organ involvement. In some patients, the response is inadequate and side effects appear from mild unpleasant up to severe toxicity. Drug metabolism and clearance may be severely compromised. Therefore, it is a priority to develop better treatments with fewer adverse events that can be used at different stages of disease activity. In recent years, a member of the tumor necrosis factor (TNF) family, soluble human B Lymphocyte Stimulator protein (BLyS), also referred to as B-cell activating factor (BAFF) and TNFSF13B has been studied extensi...
Hepatitis C virus (HCV) infection is a worldwide public health problem. Chronic infection by HCV ... more Hepatitis C virus (HCV) infection is a worldwide public health problem. Chronic infection by HCV can lead to liver cirrhosis or cancer. Although some immune-competent individuals can clear the virus, others develop chronic HCV disease due to viral mutations or an impaired immune response. IFNs type I and III and the signal transduction induced by them are essential for a proper antiviral effect. Research on the viral cycle and immune escape mechanisms have generated the basis of therapeutic strategies to achieve a sustained virological response (SVR). The first therapies were based on IFN-, then IFN-α plus ribavirin (IFN-RBV); then, pegylated-IFN--RBV (PEGIFNα-RIV) to improve cytokine pharmacokinetics. However, the maximum SVR was 60%, and several significant side effects were observed, decreasing the patients' treatment adherence. The development of direct-acting antivirals (DAAs) significantly enhanced SVR (> 90%); the compounds were able to inhibit HCV replication withou...
Nutrition is essential in developing and maintaining a robust immune system and is vital for immu... more Nutrition is essential in developing and maintaining a robust immune system and is vital for immune homeostasis. The pediatric population is particularly vulnerable to dietary changes, as their growth and development require a high energy intake. Malnutrition in infants can have immediate and long-lasting effects, increasing the risk of morbidity and mortality. Under and overnutrition can slow down the immune response to infections, which can delay recovery. To effectively defend against SARS-CoV-2 infection and enhance viral clearance, it is essential to maintain a healthy diet that includes sufficient macro and micronutrients. Several studies, most of which have been performed in adults, have shown that vitamins such as C, B12, folate, D, and E, as well as the minerals selenium, copper, iron, zinc, and magnesium, can help reduce the symptoms and duration of an infection. Supplementation with micronutrients has been shown to help with childhood malnutrition and can contribute to a more favorable clinical course of COVID-19. In children with obesity, it is also essential to monitor cardiometabolic and thrombotic risks, based on data from studies in adults. This review analyses the impact of the nutritional status of pediatric patients with SARS-CoV-2 infection, its contribution to clinical severity, and potential therapeutic interventions.
Acta Científica de la Sociedad Venezolana de Bioanalistas Especialistas, 2023
The determination of complement plays an important role in the diagnosis and follow-up of inflamm... more The determination of complement plays an important role in the diagnosis and follow-up of inflammatory and autoimmune diseases, which is why over time laboratories have intensified efforts to develop and implement techniques that allow efficient evaluation of these biomarkers. Recently, it has been proposed that for the analysisof individual complement components, plasma anticoagulated with ethylenediaminetetraacetic acid (EDTA) should be used, especially when measuring activation products, and that samples should be stored at -80ºC. However, in Venezuela most laboratories still use serum samples and only have -20ºC freezers available. Therefore, we set the following objectives: to compare the concentrations obtained for the determination of C3 and C4 using serum and plasma samples, to evaluate the performance of nephelometry and radial immunodiffusion (RID) techniques for the determination of complement C3 and C4 fractions and, finally, to determine the degree of sample affectation after the first cycle of freezing at -20ºC and thawing of the samples. For this purpose, serum and plasma samples obtained from 12 individuals were evaluated. It was evidenced that the plasma-EDTA samples showed better correlation between both techniques evaluated, the superiority of the nephelometry technique over RID was confirmed and it was demonstrated that the C3 test is less sensitive to the thawing of the samples than the determination of C4.
Humoral Immunity across the SARS-CoV-2 Spike after Sputnik V (Gam-COVID-Vac) Vaccination, 2014
SARS-CoV-2 vaccines have contributed to attenuating the burden of the COVID-19 pandemic by promot... more SARS-CoV-2 vaccines have contributed to attenuating the burden of the COVID-19 pandemic by promoting the development of effective immune responses, thus reducing the spread and severity of the pandemic. A clinical trial with the Sputnik-V vaccine was conducted in Venezuela from December 2020 to July 2021. The aim of this study was to explore the antibody reactivity of vaccinated individuals towards different regions of the spike protein (S). Neutralizing antibody (NAb) activity was assessed using a commercial surrogate assay, detecting NAbs against the receptor-binding domain (RBD), and a plaque reduction neutralization test. NAb levels were correlated with the reactivity of the antibodies to the spike regions over time. The presence of Abs against nucleoprotein was also determined to rule out the effect of exposure to the virus during the clinical trial in the serological response. A high serological reactivity was observed to S and specifically to S1 and the RBD. S2, although recognized with lower intensity by vaccinated individuals, was the subunit exhibiting the highest cross-reactivity in prepandemic sera. This study is in agreement with the high efficacy reported for the Sputnik V vaccine and shows that this vaccine is able to induce an immunity lasting for at least 180 days. The dissection of the Ab reactivity to different regions of S allowed us to identify the relevance of epitopes outside the RBD that are able to induce NAbs. This research may contribute to the understanding of vaccine immunity against SARS-CoV-2, which could contribute to the design of future vaccine strategies.
SARS-CoV-2 vaccines have contributed to attenuating the burden of the COVID-19 pandemic by promot... more SARS-CoV-2 vaccines have contributed to attenuating the burden of the COVID-19 pandemic by promoting the development of effective immune responses, thus reducing the spread and severity of the pandemic. A clinical trial with the Sputnik-V vaccine was conducted in Venezuela from December 2020 to July 2021. The aim of this study was to explore the antibody reactivity of vaccinated individuals towards different regions of the spike protein (S). Neutralizing antibody (NAb) activity was assessed using a commercial surrogate assay, detecting NAbs against the receptor-binding domain (RBD), and a plaque reduction neutralization test. NAb levels were correlated with the reactivity of the antibodies to the spike regions over time. The presence of Abs against nucleoprotein was also determined to rule out the effect of exposure to the virus during the clinical trial in the serological response. A high serological reactivity was observed to S and specifically to S1 and the RBD. S2, although recognized with lower intensity by vaccinated individuals, was the subunit exhibiting the highest cross-reactivity in prepandemic sera. This study is in agreement with the high efficacy reported for the Sputnik V vaccine and shows that this vaccine is able to induce an immunity lasting for at least 180 days. The dissection of the Ab reactivity to different regions of S allowed us to identify the relevance of epitopes outside the RBD that are able to induce NAbs. This research may contribute to the understanding of vaccine immunity against SARS-CoV-2, which could contribute to the design of future vaccine strategies.
Specific IgE tests are commonly used to evaluate food allergies. Sometimes, laboratory results ar... more Specific IgE tests are commonly used to evaluate food allergies. Sometimes, laboratory results are inconsistent with the patient´s clinical history and constitute a diagnostic and therapeutic challenge. One factor that could affect IgE reactivity results is the presence of carbohydrate cross-reacting determinants (CCDs). These carbohydrate structures present in plants and insects can induce IgE production but do not participate in the immune-mediated mechanism or the generation of allergic signs and symptoms. Objective: To determine the prevalence of CCDs in a Venezuelan mestizo population in a food-specific IgE test panel (Polycheck Allergy - Biocheck GmbH, Münster, Germany). Methods: A prospective cross-sectional descriptive study was carried out in which 100 Venezuelan mestizo patients of both sexes without age distinction who attended the laboratory service of the Instituto de Inmunología Dr Nicolas E. Bianco C. of the Universidad Central de Venezuela in the period January-April 2023. Total IgE levels were analyzed by a commercial enzyme-linked immunosorbent assay (ELISA). IgE anti-CCD and against food allergens were determined using a commercial multiplex allergen-specific IgE assay. Results: The prevalence of anti-CCD was 34 % (34). A positive correlation was observed between positive anti-CCD IgE values and positivity to multiple food allergens. The association was predominant in cereals and in males. CCD inhibitors and recombinant allergens may eliminate cross-reactive interference in vitro allergy diagnostic assays. New and specific inhibitors are important due to the high prevalence of anti-CCD in our admix population.
Hepatitis C virus (HCV) infection is a worldwide public health problem. Chronic infection with HC... more Hepatitis C virus (HCV) infection is a worldwide public health problem. Chronic infection with HCV can lead to liver cirrhosis or cancer. Although some immune-competent individuals can clear the virus, others develop chronic HCV disease due to viral mutations or an impaired immune response.IFNs type I and III and the signal transduction induced by them are essential for a proper antiviral effect. Research on the viral cycle and immune escape mechanisms has formed the basis of therapeutic strategies to achieve a sustained virological response (SVR). The first therapies were based on IFN ; then, IFN plus ribavirin (IFN–RBV); and then, pegylated-IFN -RBV (PEGIFN -RIV) to improve cytokine pharmacokinetics. However, the maximum SVR was 60%, and several significant side effects were observed, decreasing patients’ treatment adherence. The development of direct-acting antivirals (DAAs) significantly enhanced the SVR (>90%), and the compounds were able to inhibit HCV replication without significant side effects, even in paediatric populations. The management of coinfected HBV–HCV and HCV–HIV patients has also improved based on DAA and PEG-IFN -RBV (HBV–HCV). CD4 cells are crucial for an effective antiviral response. The IFN3, IL28B, TNF- , IL-10, TLR-3, and TLR-9 gene polymorphisms are involved in viral clearance, therapeutic responses, and hepatic pathologies. Future research should focus on searching for strategies to circumvent resistance-associated substitution (RAS) to DAAs, develop new therapeutic schemes for different medical conditions, including organ transplant, and develop vaccines for long-lasting cellular and humoral responses with cross-protection against different HCV genotypes. The goal is to minimise the probability of HCV infection, HCV chronicity and hepatic carcinoma.
Several studies suggest that children infected with SARS-CoV-2 have fewer clinical manifestations... more Several studies suggest that children infected with SARS-CoV-2 have fewer clinical manifestations than adults; when they develop symptoms, they rarely progress to severe disease. Different immunological theories have been proposed to explain this phenomenon. In September 2020, 16% of the active COVID-19 cases in Venezuela were children under 19 years. We conducted a cross-sectional study of pediatric patients' immune response and clinical conditions with SARS-CoV-2 infection. The patients were admitted to the COVID-19 area of the emergency department of Dr José Manuel de los Ríos Children's Hospital (2021-2022). The lymphocyte subpopulations were analysed by flow cytometry, and IFNγ, IL-6 and IL-10 serum concentrations were quantified using commercial ELISA assays. The analysis was conducted on 72 patients aged one month and 18 years. The majority, 52.8%, had mild disease, and 30.6 % were diagnosed with MIS-C. The main symptoms reported were fever, cough and diarrhoea. A cor...
SARS-CoV-2 causes the complex and heterogeneous illness known as COVID-19. The disease primarily ... more SARS-CoV-2 causes the complex and heterogeneous illness known as COVID-19. The disease primarily affects the respiratory system but can quickly become systemic, harming multiple organs and leading to long-lasting sequelae in some patients. Most infected individuals are asymptomatic or present mild symptoms. Antibodies, complement, and immune cells can efficiently eliminate the virus. However, 20% of individuals develop severe respiratory illness and multiple organ failure. Virus replication has been described in several organs in patients who died from COVID-19, suggesting a compromised immune response. Immunodeficiency and autoimmunity are responsible for this impairment and facilitate viral escape. Mutations in IFN signal transduction and T cell activation are responsible for the inadequate response in young individuals. Autoantibodies are accountable for secondary immunodeficiency in patients with severe infection or prolonged COVID-19. Antibodies against cytokines (interferons α...
In the recent years, a large number of potential biomarkers for asthma and Chronic Obstructive Pu... more In the recent years, a large number of potential biomarkers for asthma and Chronic Obstructive Pulmonary Disease (COPD) have been described. Biomarkers derive from a variety of sources (bronchioalveolar lavage fluid, sputum, exhaled breath, and blood), provide complementary information to ascertain disease diagnosis, stage, activity/progression and/or treatment responses. The present review highlights the current literature and patents in the field with potential increase in disease control and therapeutic effectiveness to be granted in the near future.
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery, 2014
In the recent years, a large number of potential biomarkers for Chronic Obstructive Pulmonary Dis... more In the recent years, a large number of potential biomarkers for Chronic Obstructive Pulmonary Disease (COPD) have been described. One of the important biomarkers is Surfactant Protein D (SPD) since serum SPD levels have been associated with lung function or health status in patients with severe COPD. Several interesting evidences of the protein and gene polymorphisms have been described. The present review highlights the current literature, recent patents and, future prospects of this important collection.
Background. One of the gene polymorphisms often studied in asthmatic patients is the β2 adrenergi... more Background. One of the gene polymorphisms often studied in asthmatic patients is the β2 adrenergic receptor (ADRβ2). Even though in the Venezuelan Mestizo population there is a high incidence of asthma, there are no direct reports of ADRβ2 gene polymorphism, and treatment response. The aim of this study was to assess, in this population, the gene frequency of ADRβ2 polymorphisms at codons 16 Arg/Gly and 27 Gln/Glu, allergen sensitization, and its relationship to bronchodilator response. Methods. Purified genomic DNA was obtained form 105 Mestizo asthmatic and 100 Mestizo healthy individuals from Venezuela. The two polymorphisms were assessed by PCR-RFLP. Patient sensitization to aeroallergens and their response to bronchodilatation were correlated. Results. Significant differences between patients and controls were recorded in: 1) the prevalence of Arg/Arg at codon 16 (28.6% in patients vs. 47% in controls, P<0.01), 2) the frequency of heterozygotes Arg/Gly (55% in patients vs. 35% in controls, P<0.01). Conversely, no differences in polymorphism frequencies were found at codon 27. The haplotypes Arg/Gly-Gln/Gln were more common in patients than controls (P <0.01), whereas the Arg/Arg-Gln/Glu combination prevailed in the control group (P<0.01). The Arg/Gly and Gln/Glu genotypes were associated with better responses after salbutamol. The asthmatic homozygotes Arg/Arg have higher sensitivity to aeroallergens. Conclusion. The difference in Arg/Arg frequency between groups suggests that this could be a protective genotype although the asthmatic group had a higher sensitivity to aeroallergens. The asthmatic heterozygotes had better bronchodilator responses than the homozygotes.
In the latest years, high quantities of biomarkers have been studied in Asthma and Chronic Obstru... more In the latest years, high quantities of biomarkers have been studied in Asthma and Chronic Obstructive Pulmonary Disease (COPD). A good biomarker should have the following characteristics: 1) clinical relevance, sensibility and specificity, c) reliability and reproducibility, d) easy to measure and to obtain. The samples in which the biomarkers can be determined are from different sources (lung biopsy, bronchoalveolar lavage, sputum, exhaled breath, urine, and blood). The biomarkers can offer complementary information in order to achieve diagnosis, stage, progression, and disease activity as well as response to treatment. In this report, we review the principal reports on biomarkers in asthma and COPD. A search for articles published between the years 1989-2013 using the Medline database. In this article we review the main biomarkers in asthma and COPD
Several studies suggest that children infected with SARS-CoV-2 have fewer clinical manifestations... more Several studies suggest that children infected with SARS-CoV-2 have fewer clinical manifestations than adults; when they develop symptoms, they rarely progress to severe disease. Different immunological theories have been proposed to explain this phenomenon. In September 2020, 16% of the active COVID-19 cases in Venezuela were children under 19 years. We conducted a cross-sectional study of pediatric patients' immune response and clinical conditions with SARS-CoV-2 infection. The patients were admitted to the COVID-19 area of the emergency department of Dr José Manuel de los Ríos Children's Hospital (2021-2022). The lymphocyte subpopulations were analysed by flow cytometry, and IFNγ, IL-6 and IL-10 serum concentrations were quantified using commercial ELISA assays. The analysis was conducted on 72 patients aged one month and 18 years. The majority, 52.8%, had mild disease, and 30.6 % were diagnosed with MIS-C. The main symptoms reported were fever, cough and diarrhoea. A correlation was found between IL-10 and IL-6 concentrations and age group; lymphocyte subpopulations and nutritional status and steroid use; IL-6 concentrations and clinical severity. The results suggest a different immune response depending on age and nutritional status that should be considered for treating pediatric COVID-19 patients.
Asthma and Chronic Obstructive Pulmonary Disease (COPD) are chronic inflammatory diseases. Both e... more Asthma and Chronic Obstructive Pulmonary Disease (COPD) are chronic inflammatory diseases. Both entities are characterized by bronchoconstriction, production of inflammatory mediators, mucus hypersecretion and inflammatory cell migration. Serotonin has immunomodulatory properties facilitating bronchoconstriction and its plasma concentration is transporter dependent (5-HTT). Mucins are glycoproteins involved in local innate immunity. The aim of this study was to assess the association between the variable number of tandem repeat polymorphisms (VNTR) of intron 2 of the serotonin ransporter (5-HTT) (STin2) and MUC7 in Venezuelan asthmatic or COPD patients. The group consisted of 301 individuals (102 asthmatics, 99 with COPD and 100 controls). There were no differences in the frequencies of MUC7 polymorphisms among the groups. However, there is a significant association between some alleles and genotypes with the presence of asthma or COPD (p <0.001). The STin2.9 allele had an odds r...
La infección por el virus SARS-CoV-2 afecta la respuesta inmune innata y adaptativa del hospedado... more La infección por el virus SARS-CoV-2 afecta la respuesta inmune innata y adaptativa del hospedador. Si la respuesta inmune innata es exacerbada, se produce la tormenta de citocinas afectando la respuesta inmune adaptativa que redunda en una disfunción del sistema inmune. El reconocimiento y eliminación viral más eficiente es por medio de los anticuerpos neutralizantes y la memoria celular adaptativa contra el virus. La memoria celular de linfocitos citotóxicos, de células NK y NKT es trascendental en la eliminación del virus y las células infectadas por éste. A la par, la memoria de células Th1 y B son críticas para la producción de anticuerpos. Sin embargo, la presencia de anticuerpos no define la respuesta celular de memoria efectiva contra el virus. Las vacunas usadas en la actualidad generan una buena respuesta CD4+ y B de memoria, pero no todas generan CD8+ de memoria. Al disminuir la respuesta de memoria CD8+ la posibilidad de manifestaciones clínicas incrementa. En pacientes ...
Autoimmune hemolytic anemia (AIHA) is an acquired heterogeneous autoimmune disorder characterized... more Autoimmune hemolytic anemia (AIHA) is an acquired heterogeneous autoimmune disorder characterized by the development of antibodies directed against antigens present on autologous erythrocytes. It is a relatively rare disease, with an estimated incidence of 1 to 3 cases in 100,000 people per year. Depending on the type and concentration of autoantibody, red blood cell destruction can occur by extravascular phagocytosis of red blood cells in the spleen, liver, and bone marrow, or by complement-mediated intravascular lysis of red blood cells. AIHA can be primary/idiopathic or secondary to infections, autoimmune diseases, malignancies, particularly lymphoproliferative disorders, and drugs. The diagnosis of AIHA should be made through a stepwise approach that aims to identify clinical and laboratory evidence of hemolysis, and then determine the immune nature of the hemolysis with the direct antiglobulin test (DAT). AIHA treatment is individualized and depends on the mechanism involved, the clinical symptoms, their severity, and the presence of comorbidities. The new treatments are directed mainly at the production of autoantibodies by the B lymphocyte compartment, at the final breakdown of erythrocytes by the complement or by the mononuclear phagocyte system and are intended for patients with refractoriness to first- and second-line treatments.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
The COVID-19 pandemic was characterized by the emergence and succession of SARSCoV-2 variants abl... more The COVID-19 pandemic was characterized by the emergence and succession of SARSCoV-2 variants able to evade the antibody response induced by natural infection and vaccination.To evaluate the IgG reactivity and neutralizing capacity of the serum of individuals vaccinated with Sputnik V (105 volunteers vaccinated) against different viral variants. IgG reactivity to the Spike protein (S) was evaluated by ELISA. A plaque reduction neutralization test was performed using different viral variant isolates. At 42 days post-vaccination, the frequency of recognition and reactivity to the S protein of the Omicron variant was lower compared to that of the other variants. In general, a higher average neutralization titer was seen against the ancestral variant compared to the variants, especially Omicron. However, some sera exhibited a higher neutralization titer to the Gamma variant compared to the ancestral variant, suggesting unapparent exposure during the clinical trial. Antibodies induced by Sputnik V can recognize, persist, and neutralize SARS-CoV-2 variants, with Omicron being the one that best evades this response. These results represent a unique report on the humoral response induced by a globally lesser-studied vaccine in terms of efficacy and immune escape, offering insights into developing vaccines targeting unknown coronaviruses.
There have been few changes over the last 50 years in the treatment of Systemic lupus erythematos... more There have been few changes over the last 50 years in the treatment of Systemic lupus erythematosus (SLE), using non-specific anti-inflammatory agents such as: non-steroidal anti-inflammatory drugs along with the immune cell modulating agent hydroxychloroquine for mild disease, and broad spectrum immunosuppressants plus anti-inflammatories such as corticosteroids, azathioprine, cyclophosphamide, or mycophenolate during flares or severe disease with organ involvement. In some patients, the response is inadequate and side effects appear from mild unpleasant up to severe toxicity. Drug metabolism and clearance may be severely compromised. Therefore, it is a priority to develop better treatments with fewer adverse events that can be used at different stages of disease activity. In recent years, a member of the tumor necrosis factor (TNF) family, soluble human B Lymphocyte Stimulator protein (BLyS), also referred to as B-cell activating factor (BAFF) and TNFSF13B has been studied extensi...
Hepatitis C virus (HCV) infection is a worldwide public health problem. Chronic infection by HCV ... more Hepatitis C virus (HCV) infection is a worldwide public health problem. Chronic infection by HCV can lead to liver cirrhosis or cancer. Although some immune-competent individuals can clear the virus, others develop chronic HCV disease due to viral mutations or an impaired immune response. IFNs type I and III and the signal transduction induced by them are essential for a proper antiviral effect. Research on the viral cycle and immune escape mechanisms have generated the basis of therapeutic strategies to achieve a sustained virological response (SVR). The first therapies were based on IFN-, then IFN-α plus ribavirin (IFN-RBV); then, pegylated-IFN--RBV (PEGIFNα-RIV) to improve cytokine pharmacokinetics. However, the maximum SVR was 60%, and several significant side effects were observed, decreasing the patients' treatment adherence. The development of direct-acting antivirals (DAAs) significantly enhanced SVR (> 90%); the compounds were able to inhibit HCV replication withou...
Nutrition is essential in developing and maintaining a robust immune system and is vital for immu... more Nutrition is essential in developing and maintaining a robust immune system and is vital for immune homeostasis. The pediatric population is particularly vulnerable to dietary changes, as their growth and development require a high energy intake. Malnutrition in infants can have immediate and long-lasting effects, increasing the risk of morbidity and mortality. Under and overnutrition can slow down the immune response to infections, which can delay recovery. To effectively defend against SARS-CoV-2 infection and enhance viral clearance, it is essential to maintain a healthy diet that includes sufficient macro and micronutrients. Several studies, most of which have been performed in adults, have shown that vitamins such as C, B12, folate, D, and E, as well as the minerals selenium, copper, iron, zinc, and magnesium, can help reduce the symptoms and duration of an infection. Supplementation with micronutrients has been shown to help with childhood malnutrition and can contribute to a more favorable clinical course of COVID-19. In children with obesity, it is also essential to monitor cardiometabolic and thrombotic risks, based on data from studies in adults. This review analyses the impact of the nutritional status of pediatric patients with SARS-CoV-2 infection, its contribution to clinical severity, and potential therapeutic interventions.
Acta Científica de la Sociedad Venezolana de Bioanalistas Especialistas, 2023
The determination of complement plays an important role in the diagnosis and follow-up of inflamm... more The determination of complement plays an important role in the diagnosis and follow-up of inflammatory and autoimmune diseases, which is why over time laboratories have intensified efforts to develop and implement techniques that allow efficient evaluation of these biomarkers. Recently, it has been proposed that for the analysisof individual complement components, plasma anticoagulated with ethylenediaminetetraacetic acid (EDTA) should be used, especially when measuring activation products, and that samples should be stored at -80ºC. However, in Venezuela most laboratories still use serum samples and only have -20ºC freezers available. Therefore, we set the following objectives: to compare the concentrations obtained for the determination of C3 and C4 using serum and plasma samples, to evaluate the performance of nephelometry and radial immunodiffusion (RID) techniques for the determination of complement C3 and C4 fractions and, finally, to determine the degree of sample affectation after the first cycle of freezing at -20ºC and thawing of the samples. For this purpose, serum and plasma samples obtained from 12 individuals were evaluated. It was evidenced that the plasma-EDTA samples showed better correlation between both techniques evaluated, the superiority of the nephelometry technique over RID was confirmed and it was demonstrated that the C3 test is less sensitive to the thawing of the samples than the determination of C4.
Humoral Immunity across the SARS-CoV-2 Spike after Sputnik V (Gam-COVID-Vac) Vaccination, 2014
SARS-CoV-2 vaccines have contributed to attenuating the burden of the COVID-19 pandemic by promot... more SARS-CoV-2 vaccines have contributed to attenuating the burden of the COVID-19 pandemic by promoting the development of effective immune responses, thus reducing the spread and severity of the pandemic. A clinical trial with the Sputnik-V vaccine was conducted in Venezuela from December 2020 to July 2021. The aim of this study was to explore the antibody reactivity of vaccinated individuals towards different regions of the spike protein (S). Neutralizing antibody (NAb) activity was assessed using a commercial surrogate assay, detecting NAbs against the receptor-binding domain (RBD), and a plaque reduction neutralization test. NAb levels were correlated with the reactivity of the antibodies to the spike regions over time. The presence of Abs against nucleoprotein was also determined to rule out the effect of exposure to the virus during the clinical trial in the serological response. A high serological reactivity was observed to S and specifically to S1 and the RBD. S2, although recognized with lower intensity by vaccinated individuals, was the subunit exhibiting the highest cross-reactivity in prepandemic sera. This study is in agreement with the high efficacy reported for the Sputnik V vaccine and shows that this vaccine is able to induce an immunity lasting for at least 180 days. The dissection of the Ab reactivity to different regions of S allowed us to identify the relevance of epitopes outside the RBD that are able to induce NAbs. This research may contribute to the understanding of vaccine immunity against SARS-CoV-2, which could contribute to the design of future vaccine strategies.
SARS-CoV-2 vaccines have contributed to attenuating the burden of the COVID-19 pandemic by promot... more SARS-CoV-2 vaccines have contributed to attenuating the burden of the COVID-19 pandemic by promoting the development of effective immune responses, thus reducing the spread and severity of the pandemic. A clinical trial with the Sputnik-V vaccine was conducted in Venezuela from December 2020 to July 2021. The aim of this study was to explore the antibody reactivity of vaccinated individuals towards different regions of the spike protein (S). Neutralizing antibody (NAb) activity was assessed using a commercial surrogate assay, detecting NAbs against the receptor-binding domain (RBD), and a plaque reduction neutralization test. NAb levels were correlated with the reactivity of the antibodies to the spike regions over time. The presence of Abs against nucleoprotein was also determined to rule out the effect of exposure to the virus during the clinical trial in the serological response. A high serological reactivity was observed to S and specifically to S1 and the RBD. S2, although recognized with lower intensity by vaccinated individuals, was the subunit exhibiting the highest cross-reactivity in prepandemic sera. This study is in agreement with the high efficacy reported for the Sputnik V vaccine and shows that this vaccine is able to induce an immunity lasting for at least 180 days. The dissection of the Ab reactivity to different regions of S allowed us to identify the relevance of epitopes outside the RBD that are able to induce NAbs. This research may contribute to the understanding of vaccine immunity against SARS-CoV-2, which could contribute to the design of future vaccine strategies.
Specific IgE tests are commonly used to evaluate food allergies. Sometimes, laboratory results ar... more Specific IgE tests are commonly used to evaluate food allergies. Sometimes, laboratory results are inconsistent with the patient´s clinical history and constitute a diagnostic and therapeutic challenge. One factor that could affect IgE reactivity results is the presence of carbohydrate cross-reacting determinants (CCDs). These carbohydrate structures present in plants and insects can induce IgE production but do not participate in the immune-mediated mechanism or the generation of allergic signs and symptoms. Objective: To determine the prevalence of CCDs in a Venezuelan mestizo population in a food-specific IgE test panel (Polycheck Allergy - Biocheck GmbH, Münster, Germany). Methods: A prospective cross-sectional descriptive study was carried out in which 100 Venezuelan mestizo patients of both sexes without age distinction who attended the laboratory service of the Instituto de Inmunología Dr Nicolas E. Bianco C. of the Universidad Central de Venezuela in the period January-April 2023. Total IgE levels were analyzed by a commercial enzyme-linked immunosorbent assay (ELISA). IgE anti-CCD and against food allergens were determined using a commercial multiplex allergen-specific IgE assay. Results: The prevalence of anti-CCD was 34 % (34). A positive correlation was observed between positive anti-CCD IgE values and positivity to multiple food allergens. The association was predominant in cereals and in males. CCD inhibitors and recombinant allergens may eliminate cross-reactive interference in vitro allergy diagnostic assays. New and specific inhibitors are important due to the high prevalence of anti-CCD in our admix population.
Hepatitis C virus (HCV) infection is a worldwide public health problem. Chronic infection with HC... more Hepatitis C virus (HCV) infection is a worldwide public health problem. Chronic infection with HCV can lead to liver cirrhosis or cancer. Although some immune-competent individuals can clear the virus, others develop chronic HCV disease due to viral mutations or an impaired immune response.IFNs type I and III and the signal transduction induced by them are essential for a proper antiviral effect. Research on the viral cycle and immune escape mechanisms has formed the basis of therapeutic strategies to achieve a sustained virological response (SVR). The first therapies were based on IFN ; then, IFN plus ribavirin (IFN–RBV); and then, pegylated-IFN -RBV (PEGIFN -RIV) to improve cytokine pharmacokinetics. However, the maximum SVR was 60%, and several significant side effects were observed, decreasing patients’ treatment adherence. The development of direct-acting antivirals (DAAs) significantly enhanced the SVR (>90%), and the compounds were able to inhibit HCV replication without significant side effects, even in paediatric populations. The management of coinfected HBV–HCV and HCV–HIV patients has also improved based on DAA and PEG-IFN -RBV (HBV–HCV). CD4 cells are crucial for an effective antiviral response. The IFN3, IL28B, TNF- , IL-10, TLR-3, and TLR-9 gene polymorphisms are involved in viral clearance, therapeutic responses, and hepatic pathologies. Future research should focus on searching for strategies to circumvent resistance-associated substitution (RAS) to DAAs, develop new therapeutic schemes for different medical conditions, including organ transplant, and develop vaccines for long-lasting cellular and humoral responses with cross-protection against different HCV genotypes. The goal is to minimise the probability of HCV infection, HCV chronicity and hepatic carcinoma.
Several studies suggest that children infected with SARS-CoV-2 have fewer clinical manifestations... more Several studies suggest that children infected with SARS-CoV-2 have fewer clinical manifestations than adults; when they develop symptoms, they rarely progress to severe disease. Different immunological theories have been proposed to explain this phenomenon. In September 2020, 16% of the active COVID-19 cases in Venezuela were children under 19 years. We conducted a cross-sectional study of pediatric patients' immune response and clinical conditions with SARS-CoV-2 infection. The patients were admitted to the COVID-19 area of the emergency department of Dr José Manuel de los Ríos Children's Hospital (2021-2022). The lymphocyte subpopulations were analysed by flow cytometry, and IFNγ, IL-6 and IL-10 serum concentrations were quantified using commercial ELISA assays. The analysis was conducted on 72 patients aged one month and 18 years. The majority, 52.8%, had mild disease, and 30.6 % were diagnosed with MIS-C. The main symptoms reported were fever, cough and diarrhoea. A cor...
SARS-CoV-2 causes the complex and heterogeneous illness known as COVID-19. The disease primarily ... more SARS-CoV-2 causes the complex and heterogeneous illness known as COVID-19. The disease primarily affects the respiratory system but can quickly become systemic, harming multiple organs and leading to long-lasting sequelae in some patients. Most infected individuals are asymptomatic or present mild symptoms. Antibodies, complement, and immune cells can efficiently eliminate the virus. However, 20% of individuals develop severe respiratory illness and multiple organ failure. Virus replication has been described in several organs in patients who died from COVID-19, suggesting a compromised immune response. Immunodeficiency and autoimmunity are responsible for this impairment and facilitate viral escape. Mutations in IFN signal transduction and T cell activation are responsible for the inadequate response in young individuals. Autoantibodies are accountable for secondary immunodeficiency in patients with severe infection or prolonged COVID-19. Antibodies against cytokines (interferons α...
In the recent years, a large number of potential biomarkers for asthma and Chronic Obstructive Pu... more In the recent years, a large number of potential biomarkers for asthma and Chronic Obstructive Pulmonary Disease (COPD) have been described. Biomarkers derive from a variety of sources (bronchioalveolar lavage fluid, sputum, exhaled breath, and blood), provide complementary information to ascertain disease diagnosis, stage, activity/progression and/or treatment responses. The present review highlights the current literature and patents in the field with potential increase in disease control and therapeutic effectiveness to be granted in the near future.
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery, 2014
In the recent years, a large number of potential biomarkers for Chronic Obstructive Pulmonary Dis... more In the recent years, a large number of potential biomarkers for Chronic Obstructive Pulmonary Disease (COPD) have been described. One of the important biomarkers is Surfactant Protein D (SPD) since serum SPD levels have been associated with lung function or health status in patients with severe COPD. Several interesting evidences of the protein and gene polymorphisms have been described. The present review highlights the current literature, recent patents and, future prospects of this important collection.
Background. One of the gene polymorphisms often studied in asthmatic patients is the β2 adrenergi... more Background. One of the gene polymorphisms often studied in asthmatic patients is the β2 adrenergic receptor (ADRβ2). Even though in the Venezuelan Mestizo population there is a high incidence of asthma, there are no direct reports of ADRβ2 gene polymorphism, and treatment response. The aim of this study was to assess, in this population, the gene frequency of ADRβ2 polymorphisms at codons 16 Arg/Gly and 27 Gln/Glu, allergen sensitization, and its relationship to bronchodilator response. Methods. Purified genomic DNA was obtained form 105 Mestizo asthmatic and 100 Mestizo healthy individuals from Venezuela. The two polymorphisms were assessed by PCR-RFLP. Patient sensitization to aeroallergens and their response to bronchodilatation were correlated. Results. Significant differences between patients and controls were recorded in: 1) the prevalence of Arg/Arg at codon 16 (28.6% in patients vs. 47% in controls, P<0.01), 2) the frequency of heterozygotes Arg/Gly (55% in patients vs. 35% in controls, P<0.01). Conversely, no differences in polymorphism frequencies were found at codon 27. The haplotypes Arg/Gly-Gln/Gln were more common in patients than controls (P <0.01), whereas the Arg/Arg-Gln/Glu combination prevailed in the control group (P<0.01). The Arg/Gly and Gln/Glu genotypes were associated with better responses after salbutamol. The asthmatic homozygotes Arg/Arg have higher sensitivity to aeroallergens. Conclusion. The difference in Arg/Arg frequency between groups suggests that this could be a protective genotype although the asthmatic group had a higher sensitivity to aeroallergens. The asthmatic heterozygotes had better bronchodilator responses than the homozygotes.
In the latest years, high quantities of biomarkers have been studied in Asthma and Chronic Obstru... more In the latest years, high quantities of biomarkers have been studied in Asthma and Chronic Obstructive Pulmonary Disease (COPD). A good biomarker should have the following characteristics: 1) clinical relevance, sensibility and specificity, c) reliability and reproducibility, d) easy to measure and to obtain. The samples in which the biomarkers can be determined are from different sources (lung biopsy, bronchoalveolar lavage, sputum, exhaled breath, urine, and blood). The biomarkers can offer complementary information in order to achieve diagnosis, stage, progression, and disease activity as well as response to treatment. In this report, we review the principal reports on biomarkers in asthma and COPD. A search for articles published between the years 1989-2013 using the Medline database. In this article we review the main biomarkers in asthma and COPD
Several studies suggest that children infected with SARS-CoV-2 have fewer clinical manifestations... more Several studies suggest that children infected with SARS-CoV-2 have fewer clinical manifestations than adults; when they develop symptoms, they rarely progress to severe disease. Different immunological theories have been proposed to explain this phenomenon. In September 2020, 16% of the active COVID-19 cases in Venezuela were children under 19 years. We conducted a cross-sectional study of pediatric patients' immune response and clinical conditions with SARS-CoV-2 infection. The patients were admitted to the COVID-19 area of the emergency department of Dr José Manuel de los Ríos Children's Hospital (2021-2022). The lymphocyte subpopulations were analysed by flow cytometry, and IFNγ, IL-6 and IL-10 serum concentrations were quantified using commercial ELISA assays. The analysis was conducted on 72 patients aged one month and 18 years. The majority, 52.8%, had mild disease, and 30.6 % were diagnosed with MIS-C. The main symptoms reported were fever, cough and diarrhoea. A correlation was found between IL-10 and IL-6 concentrations and age group; lymphocyte subpopulations and nutritional status and steroid use; IL-6 concentrations and clinical severity. The results suggest a different immune response depending on age and nutritional status that should be considered for treating pediatric COVID-19 patients.
Asthma and Chronic Obstructive Pulmonary Disease (COPD) are chronic inflammatory diseases. Both e... more Asthma and Chronic Obstructive Pulmonary Disease (COPD) are chronic inflammatory diseases. Both entities are characterized by bronchoconstriction, production of inflammatory mediators, mucus hypersecretion and inflammatory cell migration. Serotonin has immunomodulatory properties facilitating bronchoconstriction and its plasma concentration is transporter dependent (5-HTT). Mucins are glycoproteins involved in local innate immunity. The aim of this study was to assess the association between the variable number of tandem repeat polymorphisms (VNTR) of intron 2 of the serotonin ransporter (5-HTT) (STin2) and MUC7 in Venezuelan asthmatic or COPD patients. The group consisted of 301 individuals (102 asthmatics, 99 with COPD and 100 controls). There were no differences in the frequencies of MUC7 polymorphisms among the groups. However, there is a significant association between some alleles and genotypes with the presence of asthma or COPD (p <0.001). The STin2.9 allele had an odds r...
La infección por el virus SARS-CoV-2 afecta la respuesta inmune innata y adaptativa del hospedado... more La infección por el virus SARS-CoV-2 afecta la respuesta inmune innata y adaptativa del hospedador. Si la respuesta inmune innata es exacerbada, se produce la tormenta de citocinas afectando la respuesta inmune adaptativa que redunda en una disfunción del sistema inmune. El reconocimiento y eliminación viral más eficiente es por medio de los anticuerpos neutralizantes y la memoria celular adaptativa contra el virus. La memoria celular de linfocitos citotóxicos, de células NK y NKT es trascendental en la eliminación del virus y las células infectadas por éste. A la par, la memoria de células Th1 y B son críticas para la producción de anticuerpos. Sin embargo, la presencia de anticuerpos no define la respuesta celular de memoria efectiva contra el virus. Las vacunas usadas en la actualidad generan una buena respuesta CD4+ y B de memoria, pero no todas generan CD8+ de memoria. Al disminuir la respuesta de memoria CD8+ la posibilidad de manifestaciones clínicas incrementa. En pacientes ...
Autoimmune hemolytic anemia (AIHA) is an acquired heterogeneous autoimmune disorder characterized... more Autoimmune hemolytic anemia (AIHA) is an acquired heterogeneous autoimmune disorder characterized by the development of antibodies directed against antigens present on autologous erythrocytes. It is a relatively rare disease, with an estimated incidence of 1 to 3 cases in 100,000 people per year. Depending on the type and concentration of autoantibody, red blood cell destruction can occur by extravascular phagocytosis of red blood cells in the spleen, liver, and bone marrow, or by complement-mediated intravascular lysis of red blood cells. AIHA can be primary/idiopathic or secondary to infections, autoimmune diseases, malignancies, particularly lymphoproliferative disorders, and drugs. The diagnosis of AIHA should be made through a stepwise approach that aims to identify clinical and laboratory evidence of hemolysis, and then determine the immune nature of the hemolysis with the direct antiglobulin test (DAT). AIHA treatment is individualized and depends on the mechanism involved, the clinical symptoms, their severity, and the presence of comorbidities. The new treatments are directed mainly at the production of autoantibodies by the B lymphocyte compartment, at the final breakdown of erythrocytes by the complement or by the mononuclear phagocyte system and are intended for patients with refractoriness to first- and second-line treatments.
Since the emergence of COVID-19 there have been case reports with development of autoimmune or au... more Since the emergence of COVID-19 there have been case reports with development of autoimmune or autoinflammatory conditions following acute infection and the presence of various systemic and organ specific autoantibodies in patients following the infection, especially the presence of antiphospholipid antibodies (APA). SARS-Co-2 has the ability to induce a state of hyperstimulation with increased synthesis of multiple autoantibodies, demonstrated in different studies evaluating the presence of autoantibodies This systemic autoreactivity suggests autoimmune activation during and/or following SARS-CoV-2 infection. Researchers studied APA levels in post-acute COVID-19 finding increased levels of anti-B2 glycoprotein I, anti-Annexin V, antiprothrombin, with no correlation with thrombotic events. Furthermore, this persistent positivity of autoantibodies has led to the conclusion that, in a group of people, production is maintained and may lead to the symptoms of long COVID. Our study evaluated the presence of post COVID-19 symptoms and autoantibody positivity in convalescent patients.
Uploads
Papers by Alexis García
reactivity to the S protein of the Omicron variant was lower compared to that of the other variants.
In general, a higher average neutralization titer was seen against the ancestral variant compared to the variants, especially Omicron. However, some sera exhibited a higher neutralization titer to the Gamma variant compared to the ancestral variant, suggesting unapparent exposure during the clinical trial. Antibodies induced by Sputnik V can recognize, persist, and neutralize SARS-CoV-2 variants, with Omicron being the one that best evades this response. These results represent a unique report on the humoral response induced by a globally lesser-studied vaccine in terms of efficacy and immune escape, offering insights into developing vaccines targeting unknown coronaviruses.
copper, iron, zinc, and magnesium, can help reduce the symptoms and duration of an infection. Supplementation with micronutrients has been shown to help with childhood malnutrition and can contribute to a more favorable clinical course of COVID-19. In children with obesity, it is also
essential to monitor cardiometabolic and thrombotic risks, based on data from studies in adults. This review analyses the impact of the nutritional status of pediatric patients with SARS-CoV-2 infection, its contribution to clinical severity, and potential therapeutic interventions.
techniques that allow efficient evaluation of these biomarkers. Recently, it has been proposed that for the analysisof individual complement components, plasma anticoagulated with ethylenediaminetetraacetic acid (EDTA) should be used, especially when measuring activation products, and that samples should be stored at -80ºC. However, in Venezuela most laboratories still use serum samples and only have -20ºC freezers available. Therefore, we set the following objectives: to compare the concentrations obtained for the determination of C3 and C4 using serum and plasma samples, to evaluate the performance of nephelometry and radial immunodiffusion (RID) techniques for the determination of complement C3 and C4 fractions and, finally, to determine the degree of sample affectation after the first cycle of freezing at -20ºC and thawing of the samples. For this purpose, serum and plasma samples obtained
from 12 individuals were evaluated. It was evidenced that the plasma-EDTA samples showed better correlation between both techniques evaluated, the superiority of the nephelometry technique over RID was confirmed and it was demonstrated that the C3 test is less sensitive to the thawing of the samples than the determination of C4.
strategies to achieve a sustained virological response (SVR). The first therapies were based on IFN ; then, IFN plus ribavirin (IFN–RBV); and then, pegylated-IFN -RBV (PEGIFN -RIV) to improve cytokine
pharmacokinetics. However, the maximum SVR was 60%, and several significant side effects were observed, decreasing patients’ treatment adherence. The development of direct-acting antivirals (DAAs)
significantly enhanced the SVR (>90%), and the compounds were able to inhibit HCV replication without significant side effects, even in paediatric populations. The management of coinfected HBV–HCV and HCV–HIV patients has also improved based on DAA and PEG-IFN -RBV (HBV–HCV). CD4 cells are crucial for an effective antiviral response. The IFN3, IL28B, TNF- , IL-10, TLR-3, and TLR-9 gene polymorphisms are involved in viral clearance, therapeutic responses, and hepatic pathologies. Future
research should focus on searching for strategies to circumvent resistance-associated substitution (RAS) to DAAs, develop new therapeutic schemes for different medical conditions, including organ transplant, and develop vaccines for long-lasting cellular and humoral responses with cross-protection against different HCV genotypes. The goal is to minimise the probability of HCV infection, HCV chronicity and
hepatic carcinoma.
or by complement-mediated intravascular lysis of red blood cells. AIHA can be primary/idiopathic or secondary to infections, autoimmune diseases, malignancies, particularly lymphoproliferative disorders, and drugs. The diagnosis of AIHA should be made through a stepwise approach that aims to identify clinical and laboratory evidence of hemolysis, and then determine the immune nature of the hemolysis with
the direct antiglobulin test (DAT). AIHA treatment is individualized and depends on the mechanism involved, the clinical symptoms, their severity, and the presence of comorbidities. The new treatments are directed
mainly at the production of autoantibodies by the B lymphocyte compartment, at the final breakdown of erythrocytes by the complement or by the mononuclear phagocyte system and are intended for patients with refractoriness to first- and second-line treatments.
reactivity to the S protein of the Omicron variant was lower compared to that of the other variants.
In general, a higher average neutralization titer was seen against the ancestral variant compared to the variants, especially Omicron. However, some sera exhibited a higher neutralization titer to the Gamma variant compared to the ancestral variant, suggesting unapparent exposure during the clinical trial. Antibodies induced by Sputnik V can recognize, persist, and neutralize SARS-CoV-2 variants, with Omicron being the one that best evades this response. These results represent a unique report on the humoral response induced by a globally lesser-studied vaccine in terms of efficacy and immune escape, offering insights into developing vaccines targeting unknown coronaviruses.
copper, iron, zinc, and magnesium, can help reduce the symptoms and duration of an infection. Supplementation with micronutrients has been shown to help with childhood malnutrition and can contribute to a more favorable clinical course of COVID-19. In children with obesity, it is also
essential to monitor cardiometabolic and thrombotic risks, based on data from studies in adults. This review analyses the impact of the nutritional status of pediatric patients with SARS-CoV-2 infection, its contribution to clinical severity, and potential therapeutic interventions.
techniques that allow efficient evaluation of these biomarkers. Recently, it has been proposed that for the analysisof individual complement components, plasma anticoagulated with ethylenediaminetetraacetic acid (EDTA) should be used, especially when measuring activation products, and that samples should be stored at -80ºC. However, in Venezuela most laboratories still use serum samples and only have -20ºC freezers available. Therefore, we set the following objectives: to compare the concentrations obtained for the determination of C3 and C4 using serum and plasma samples, to evaluate the performance of nephelometry and radial immunodiffusion (RID) techniques for the determination of complement C3 and C4 fractions and, finally, to determine the degree of sample affectation after the first cycle of freezing at -20ºC and thawing of the samples. For this purpose, serum and plasma samples obtained
from 12 individuals were evaluated. It was evidenced that the plasma-EDTA samples showed better correlation between both techniques evaluated, the superiority of the nephelometry technique over RID was confirmed and it was demonstrated that the C3 test is less sensitive to the thawing of the samples than the determination of C4.
strategies to achieve a sustained virological response (SVR). The first therapies were based on IFN ; then, IFN plus ribavirin (IFN–RBV); and then, pegylated-IFN -RBV (PEGIFN -RIV) to improve cytokine
pharmacokinetics. However, the maximum SVR was 60%, and several significant side effects were observed, decreasing patients’ treatment adherence. The development of direct-acting antivirals (DAAs)
significantly enhanced the SVR (>90%), and the compounds were able to inhibit HCV replication without significant side effects, even in paediatric populations. The management of coinfected HBV–HCV and HCV–HIV patients has also improved based on DAA and PEG-IFN -RBV (HBV–HCV). CD4 cells are crucial for an effective antiviral response. The IFN3, IL28B, TNF- , IL-10, TLR-3, and TLR-9 gene polymorphisms are involved in viral clearance, therapeutic responses, and hepatic pathologies. Future
research should focus on searching for strategies to circumvent resistance-associated substitution (RAS) to DAAs, develop new therapeutic schemes for different medical conditions, including organ transplant, and develop vaccines for long-lasting cellular and humoral responses with cross-protection against different HCV genotypes. The goal is to minimise the probability of HCV infection, HCV chronicity and
hepatic carcinoma.
or by complement-mediated intravascular lysis of red blood cells. AIHA can be primary/idiopathic or secondary to infections, autoimmune diseases, malignancies, particularly lymphoproliferative disorders, and drugs. The diagnosis of AIHA should be made through a stepwise approach that aims to identify clinical and laboratory evidence of hemolysis, and then determine the immune nature of the hemolysis with
the direct antiglobulin test (DAT). AIHA treatment is individualized and depends on the mechanism involved, the clinical symptoms, their severity, and the presence of comorbidities. The new treatments are directed
mainly at the production of autoantibodies by the B lymphocyte compartment, at the final breakdown of erythrocytes by the complement or by the mononuclear phagocyte system and are intended for patients with refractoriness to first- and second-line treatments.