<strong>INTRODUCTION AND AIM</strong> Primary Immune Deficiencies (PID) are rare but ... more <strong>INTRODUCTION AND AIM</strong> Primary Immune Deficiencies (PID) are rare but very severe hereditary pathologies associated with disfunction of immune system. The most common type of PID is Antibody Deficiencies (AD) that characterized by the recurrent bacterial infections in gastrointestinal, respiratory and urinary tract. The aim of the study was to analyze the data of pediatric and adult patients diagnosed as AD in our PID center between 2010-2019. <strong>METHODS</strong> All patients with PID were examinated by blood chemistry and phenotyping of immune cells in peripheral blood, measurement of IgM, IgG, IgA, IgE and sIgA levels in serum and saliva, phagocytic activity by NBT, and detection of CIC by photometric method. Additional X-ray and ultrasound examinations were also performed. <strong>RESULT </strong> In 2010-2020 years in Research Immunology laboratory of Azerbaijan Medical University patients suspected to immune disorders were examinated and the Antibody deficiency was detected in 46 patients: 3 adult and 6 children in age of 2-8 years were diagnosed with sIgA deficiency, Hyper IgM syndrome was rare deficiency-only in 2 chidren in age 1-2 years. The biggest group of patients with common variable immune deficiency and agammaglobulinemia included children of different ages and adults. All the patients who had frequent and severe infections-lung, skin, gastrointestinal diseases, were receiving replacement therapy-IVIG. Immune disbalance show decrease of quantity and function of B-cell, hypogammaglobulinemia. Detaled diagnosis in 5 patients based on the genetic tests which were carried out. The following results show genetic mutations: 2 case –Btk deficiency, 2 cases - CD40 LG deficiency, 1 case - BLNK gene mutation. <strong>CONCLUSION</strong> The children with repeated, severe bacterial infections and hypoglobulinemia have to be suspected on PID especially to AD type. Immune examination should be including serum immunoglobulin levels and B and T-cell subsets in peripheral blood as the first sta [...]
Hemoglobinopathies, including sickle cell disease (SCD) and thalassemia syndromes, represent the ... more Hemoglobinopathies, including sickle cell disease (SCD) and thalassemia syndromes, represent the commonest monogenic diseases in the world. Although their pathogenicity is well established, the diverse clinical manifestations and the varying degree of severity are less understood and are thought to be governed, in part, by genetic modifiers. Despite the identification and characterization of a few genetic modifiers by previous studies, these are as yet insufficient to guide treatment recommendations or stratify patients reliably. Larger, multi-ethnic studies are needed to identify and validate further disease modifiers that can be used for patient stratification and personalized treatment. There is a growing need for deeper insight with the availability of novel targeted therapies and potentially curative options like gene therapy in both SCD and thalassemia. The International Hemoglobinopathy Research Network (INHERENT) is a recently established network with the aim of investigatin...
Background Patients with hematological malignancies (HM) are at high risk of mortality from SARS-... more Background Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778...
With the carrier rate of 4%-8.6%, β-thalassemia is one of the most prevalent hereditary disorders... more With the carrier rate of 4%-8.6%, β-thalassemia is one of the most prevalent hereditary disorders in Azerbaijan. Taking into consideration the high frequency of β-thalassemia as well as the occurrences of several other hemoglobinopathies, we conducted a large genotyping study to investigate the mutational background of common hemoglobinopathies in the country. A-and β-globin genes were evaluated in the carriers of mutations identified via hematological indices and hemoglobin fractions (n = 1,757). Genotyping of β-thalassemia carriers identified through population screening revealed 32 mutations, with codon 8 [-AA]-34.96%, IVS-II-1 [G > A]-16.35%, and IVS-I-110 [G > A]-10.12% leading the spectrum. Analysis of associations of β-thalassemia mutations with geographical regions of the country identified the strongest association between codon 8 [-AA] and Shaki-Zaqatala, and codon 5 [-CT] in Mountainous Shirvan regions (ri > 6.00; p < 0.05). HbS, HbD-Punjab, and HbE were the most prevalent among our variant hemoglobin cohort, commonly inherited in compounds with β-thalassemia than in the homozygous state. We identified nine α-thalassemia mutations, 20.5 kb and 3.7 kb deletions together accounting for 74% of the spectrum. Point mutations of α-thalassemia were less common among our observations and were mainly inherited in compounds with deletions. Our results allow a better understanding of the wide spectrum of mutations in Azerbaijan and highlights the high heterogeneity of hemoglobinopathies in the local population.
Background: Transcaucasia is a geographical region located on the border of Eastern Europe and We... more Background: Transcaucasia is a geographical region located on the border of Eastern Europe and Western Asia including territories of Azerbaijan, Georgia and Armenia. The region has long been known for high incidence of thalassemia and previous studies reported the highest prevalence of β-thalassemia in Azerbaijan (AZE - 4-5%, GEO - 3%, ARM - 2%) and an overlapping mutation spectrum within the region. Nevertheless, the characteristic genotypes and mutation spectrum of less recognised α-thalassemia have not been reported by far. In this multicentre cross-sectional study, we analysed the genotypes of α-thalassemia patients from Azerbaijan as representative of the region. Methods: 45 patients diagnosed with HbH disease, β-thalassemia major with milder clinical manifestations or any other clinical condition with possible inheritance of α-thalassemia mutations were included in the study. Clinically significant deletions as well as point mutations located on the HBA1 and HBA2 genes were id...
We identified a novel mutation of b-thalassemia (b-thal) in a heterozygous carrier from Azerbaija... more We identified a novel mutation of b-thalassemia (b-thal) in a heterozygous carrier from Azerbaijan. Phenotypical data and molecular mechanisms of codon 2 (-T) (HBB: c.9delT) was relevant to b 0-thal. Additionally, we here report two new mutations on the HBB gene, not observed previously, in the local population as well as a non causative promoter mutation-198 (A>G) (HBB: c.-248A>G).
Clinical Chemistry and Laboratory Medicine (CCLM), 2018
Thalassemia is one of the most common hereditary disorders of the developing world, and it is ass... more Thalassemia is one of the most common hereditary disorders of the developing world, and it is associated with severe anemia and transfusion dependence. The global health burden of thalassemia has increased as a result of human mobility and migration in recent years. Depending on inherited mutations, thalassemia patients exhibit distorted hemoglobin (Hb) patterns and deviated red cell indices, both of which can be used to support identification by diagnostic tools. Diagnostic approaches vary depending on the target population and the aim of the testing. Current methods, which are based on Hb patterns, are used for first-line screening, whereas molecular testing is needed for conformation of the results and for prenatal and preimplantation genetic diagnosis. In the present paper, we review the diagnostic parameters, pitfalls, interfering factors, and methods; currently available best-practice guidelines; quality assurance and standardization of the procedures; and promising laboratory...
Codon 14 (þT) (HBB: c.44_45insT) is a very rare b-thalassemia (b-thal) mutation previously report... more Codon 14 (þT) (HBB: c.44_45insT) is a very rare b-thalassemia (b-thal) mutation previously reported in three b-thal major (b-TM) patients of Azerbaijani origin. None of the previous reports described the genotype-phenotype correlation of the mutation. We here report the first case of homozygous codon 14 together with data of the heterozygous parents.
The -92 (C>T) (HBB: c.-142C>T) is a silent β-thalassemia (β-thal) mutation previously descr... more The -92 (C>T) (HBB: c.-142C>T) is a silent β-thalassemia (β-thal) mutation previously described in combination with several β mutations and expressed as β-thal intermedia (β-TI). Heterozygous individuals are known to be completely asymptomatic showing borderline hemoglobin (Hb), mean corpuscular volume (MCV) and Hb A levels. Here, we report the first incidence of -92 in Eastern Europe and in Azerbaijan, and the first case in combination with codons 36/37 (-T) (HBB: c.112delT) mutation.
Cardiovascular & hematological agents in medicinal chemistry, Jan 28, 2017
Thiopurine S-methyltransferase (TPMT) enzyme metabolizes thiopurine drugs which are widely used i... more Thiopurine S-methyltransferase (TPMT) enzyme metabolizes thiopurine drugs which are widely used in various disciplines as well as in leukemias. Individual enzyme activity varies depending on the genetic polymorphisms of TPMT gene located at chromosome 6. Up to 14% of population is known to have a decreased enzyme activity, and if treated with standard doses of thiopurines, these individuals are at the high risk of severe adverse drug reactions (ADR) as myelosuppression, gastrointestinal intolerance, pancreatitis and hypersensitivity. However, TPMT-deficient patients can successfully be treated with decreased thiopurine doses if enzyme status is identified by a prior testing. TPMT status identification is a pioneering experience in an application of a pharmacogenetic testing in clinical settings. 4 TPMT (*2,*3A, *3B, *3C) alleles are known to account for 80-95% of a decreased enzyme activity, and therefore, identifying the presence of these alleles supported by phenotypic measurement...
β-Talasemi Azerbaycan'da görülen en sık kalıtsal hastalıktır. Çalışmamızın amacı Azerbaycan popül... more β-Talasemi Azerbaycan'da görülen en sık kalıtsal hastalıktır. Çalışmamızın amacı Azerbaycan popülasyonunda en sık görülen β-talasemi mutasyonlarının genotip-fenotip korelasyonlarının ortaya çıkarılmasıydı. Yerel popülasyonda en sık görülen β-globin gen mutasyonları olan kodon 8 (-AA), IVS-I-6 (T>C) ve IVS-II-1 (G>A) mutasyonlarını taşıyan hastalar hematolojik parametreler açısından değerlendirildi. Daha önceden test edilmiş ve genotipik özellikleri bilinen 55 hasta çalışmaya dahil edildi. Mutasyonların fenotipik manifestasyonlarının gösterilmesi için hematolojik indeksler ve hemoglobin fraksiyonlarına bakıldı. Sonuçlar farklı β-globin gen mutasyonları arasında klinik başvuru açısından farklılıklar olduğunu göstermekteydi: IVS-I-6 (T>C) mutasyonu olan bireylerde hastalık kodon 8 (-AA) ve IVS-II-1 (G>A) mutasyonu olanlara göre daha hafif seyretmekteydi. Erken genotipik tanımlama klinik başvuru özelliklerinin tahmin edilmesine ve hastalara en iyi terapötik yaklaşımların uygulanmasına yardımcı olabilir.
β-Thalassemia intermedia is a clinical condition of intermediate gravity between β-thalassemia mi... more β-Thalassemia intermedia is a clinical condition of intermediate gravity between β-thalassemia minor, the asymptomatic carrier, and β-thalassemia major, the transfusion-dependent severe anemia. It is characterized by a significant clinical polymorphism, which is attributable to its genetic heterogeneity. Ineffective erythropoiesis, chronic anemia, and iron overload contribute to the clinical complications of thalassemia intermedia through stepwise pathophysiological mechanisms. These complications, including splenomegaly, extramedullary erythropoiesis, iron accumulation, leg ulcers, thrombophilia, and bone abnormalities can be managed via fetal hemoglobin induction, occasional transfusions, chelation, and in some cases, stem cell transplantation. Given its clinical diversity, thalassemia intermedia patients require tailored approaches to therapy. Here we present an overview and novel approaches to the genetic basis, pathophysiological mechanisms, clinical complications, and optimal ...
<strong>INTRODUCTION AND AIM</strong> Primary Immune Deficiencies (PID) are rare but ... more <strong>INTRODUCTION AND AIM</strong> Primary Immune Deficiencies (PID) are rare but very severe hereditary pathologies associated with disfunction of immune system. The most common type of PID is Antibody Deficiencies (AD) that characterized by the recurrent bacterial infections in gastrointestinal, respiratory and urinary tract. The aim of the study was to analyze the data of pediatric and adult patients diagnosed as AD in our PID center between 2010-2019. <strong>METHODS</strong> All patients with PID were examinated by blood chemistry and phenotyping of immune cells in peripheral blood, measurement of IgM, IgG, IgA, IgE and sIgA levels in serum and saliva, phagocytic activity by NBT, and detection of CIC by photometric method. Additional X-ray and ultrasound examinations were also performed. <strong>RESULT </strong> In 2010-2020 years in Research Immunology laboratory of Azerbaijan Medical University patients suspected to immune disorders were examinated and the Antibody deficiency was detected in 46 patients: 3 adult and 6 children in age of 2-8 years were diagnosed with sIgA deficiency, Hyper IgM syndrome was rare deficiency-only in 2 chidren in age 1-2 years. The biggest group of patients with common variable immune deficiency and agammaglobulinemia included children of different ages and adults. All the patients who had frequent and severe infections-lung, skin, gastrointestinal diseases, were receiving replacement therapy-IVIG. Immune disbalance show decrease of quantity and function of B-cell, hypogammaglobulinemia. Detaled diagnosis in 5 patients based on the genetic tests which were carried out. The following results show genetic mutations: 2 case –Btk deficiency, 2 cases - CD40 LG deficiency, 1 case - BLNK gene mutation. <strong>CONCLUSION</strong> The children with repeated, severe bacterial infections and hypoglobulinemia have to be suspected on PID especially to AD type. Immune examination should be including serum immunoglobulin levels and B and T-cell subsets in peripheral blood as the first sta [...]
Hemoglobinopathies, including sickle cell disease (SCD) and thalassemia syndromes, represent the ... more Hemoglobinopathies, including sickle cell disease (SCD) and thalassemia syndromes, represent the commonest monogenic diseases in the world. Although their pathogenicity is well established, the diverse clinical manifestations and the varying degree of severity are less understood and are thought to be governed, in part, by genetic modifiers. Despite the identification and characterization of a few genetic modifiers by previous studies, these are as yet insufficient to guide treatment recommendations or stratify patients reliably. Larger, multi-ethnic studies are needed to identify and validate further disease modifiers that can be used for patient stratification and personalized treatment. There is a growing need for deeper insight with the availability of novel targeted therapies and potentially curative options like gene therapy in both SCD and thalassemia. The International Hemoglobinopathy Research Network (INHERENT) is a recently established network with the aim of investigatin...
Background Patients with hematological malignancies (HM) are at high risk of mortality from SARS-... more Background Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778...
With the carrier rate of 4%-8.6%, β-thalassemia is one of the most prevalent hereditary disorders... more With the carrier rate of 4%-8.6%, β-thalassemia is one of the most prevalent hereditary disorders in Azerbaijan. Taking into consideration the high frequency of β-thalassemia as well as the occurrences of several other hemoglobinopathies, we conducted a large genotyping study to investigate the mutational background of common hemoglobinopathies in the country. A-and β-globin genes were evaluated in the carriers of mutations identified via hematological indices and hemoglobin fractions (n = 1,757). Genotyping of β-thalassemia carriers identified through population screening revealed 32 mutations, with codon 8 [-AA]-34.96%, IVS-II-1 [G > A]-16.35%, and IVS-I-110 [G > A]-10.12% leading the spectrum. Analysis of associations of β-thalassemia mutations with geographical regions of the country identified the strongest association between codon 8 [-AA] and Shaki-Zaqatala, and codon 5 [-CT] in Mountainous Shirvan regions (ri > 6.00; p < 0.05). HbS, HbD-Punjab, and HbE were the most prevalent among our variant hemoglobin cohort, commonly inherited in compounds with β-thalassemia than in the homozygous state. We identified nine α-thalassemia mutations, 20.5 kb and 3.7 kb deletions together accounting for 74% of the spectrum. Point mutations of α-thalassemia were less common among our observations and were mainly inherited in compounds with deletions. Our results allow a better understanding of the wide spectrum of mutations in Azerbaijan and highlights the high heterogeneity of hemoglobinopathies in the local population.
Background: Transcaucasia is a geographical region located on the border of Eastern Europe and We... more Background: Transcaucasia is a geographical region located on the border of Eastern Europe and Western Asia including territories of Azerbaijan, Georgia and Armenia. The region has long been known for high incidence of thalassemia and previous studies reported the highest prevalence of β-thalassemia in Azerbaijan (AZE - 4-5%, GEO - 3%, ARM - 2%) and an overlapping mutation spectrum within the region. Nevertheless, the characteristic genotypes and mutation spectrum of less recognised α-thalassemia have not been reported by far. In this multicentre cross-sectional study, we analysed the genotypes of α-thalassemia patients from Azerbaijan as representative of the region. Methods: 45 patients diagnosed with HbH disease, β-thalassemia major with milder clinical manifestations or any other clinical condition with possible inheritance of α-thalassemia mutations were included in the study. Clinically significant deletions as well as point mutations located on the HBA1 and HBA2 genes were id...
We identified a novel mutation of b-thalassemia (b-thal) in a heterozygous carrier from Azerbaija... more We identified a novel mutation of b-thalassemia (b-thal) in a heterozygous carrier from Azerbaijan. Phenotypical data and molecular mechanisms of codon 2 (-T) (HBB: c.9delT) was relevant to b 0-thal. Additionally, we here report two new mutations on the HBB gene, not observed previously, in the local population as well as a non causative promoter mutation-198 (A>G) (HBB: c.-248A>G).
Clinical Chemistry and Laboratory Medicine (CCLM), 2018
Thalassemia is one of the most common hereditary disorders of the developing world, and it is ass... more Thalassemia is one of the most common hereditary disorders of the developing world, and it is associated with severe anemia and transfusion dependence. The global health burden of thalassemia has increased as a result of human mobility and migration in recent years. Depending on inherited mutations, thalassemia patients exhibit distorted hemoglobin (Hb) patterns and deviated red cell indices, both of which can be used to support identification by diagnostic tools. Diagnostic approaches vary depending on the target population and the aim of the testing. Current methods, which are based on Hb patterns, are used for first-line screening, whereas molecular testing is needed for conformation of the results and for prenatal and preimplantation genetic diagnosis. In the present paper, we review the diagnostic parameters, pitfalls, interfering factors, and methods; currently available best-practice guidelines; quality assurance and standardization of the procedures; and promising laboratory...
Codon 14 (þT) (HBB: c.44_45insT) is a very rare b-thalassemia (b-thal) mutation previously report... more Codon 14 (þT) (HBB: c.44_45insT) is a very rare b-thalassemia (b-thal) mutation previously reported in three b-thal major (b-TM) patients of Azerbaijani origin. None of the previous reports described the genotype-phenotype correlation of the mutation. We here report the first case of homozygous codon 14 together with data of the heterozygous parents.
The -92 (C>T) (HBB: c.-142C>T) is a silent β-thalassemia (β-thal) mutation previously descr... more The -92 (C>T) (HBB: c.-142C>T) is a silent β-thalassemia (β-thal) mutation previously described in combination with several β mutations and expressed as β-thal intermedia (β-TI). Heterozygous individuals are known to be completely asymptomatic showing borderline hemoglobin (Hb), mean corpuscular volume (MCV) and Hb A levels. Here, we report the first incidence of -92 in Eastern Europe and in Azerbaijan, and the first case in combination with codons 36/37 (-T) (HBB: c.112delT) mutation.
Cardiovascular & hematological agents in medicinal chemistry, Jan 28, 2017
Thiopurine S-methyltransferase (TPMT) enzyme metabolizes thiopurine drugs which are widely used i... more Thiopurine S-methyltransferase (TPMT) enzyme metabolizes thiopurine drugs which are widely used in various disciplines as well as in leukemias. Individual enzyme activity varies depending on the genetic polymorphisms of TPMT gene located at chromosome 6. Up to 14% of population is known to have a decreased enzyme activity, and if treated with standard doses of thiopurines, these individuals are at the high risk of severe adverse drug reactions (ADR) as myelosuppression, gastrointestinal intolerance, pancreatitis and hypersensitivity. However, TPMT-deficient patients can successfully be treated with decreased thiopurine doses if enzyme status is identified by a prior testing. TPMT status identification is a pioneering experience in an application of a pharmacogenetic testing in clinical settings. 4 TPMT (*2,*3A, *3B, *3C) alleles are known to account for 80-95% of a decreased enzyme activity, and therefore, identifying the presence of these alleles supported by phenotypic measurement...
β-Talasemi Azerbaycan'da görülen en sık kalıtsal hastalıktır. Çalışmamızın amacı Azerbaycan popül... more β-Talasemi Azerbaycan'da görülen en sık kalıtsal hastalıktır. Çalışmamızın amacı Azerbaycan popülasyonunda en sık görülen β-talasemi mutasyonlarının genotip-fenotip korelasyonlarının ortaya çıkarılmasıydı. Yerel popülasyonda en sık görülen β-globin gen mutasyonları olan kodon 8 (-AA), IVS-I-6 (T>C) ve IVS-II-1 (G>A) mutasyonlarını taşıyan hastalar hematolojik parametreler açısından değerlendirildi. Daha önceden test edilmiş ve genotipik özellikleri bilinen 55 hasta çalışmaya dahil edildi. Mutasyonların fenotipik manifestasyonlarının gösterilmesi için hematolojik indeksler ve hemoglobin fraksiyonlarına bakıldı. Sonuçlar farklı β-globin gen mutasyonları arasında klinik başvuru açısından farklılıklar olduğunu göstermekteydi: IVS-I-6 (T>C) mutasyonu olan bireylerde hastalık kodon 8 (-AA) ve IVS-II-1 (G>A) mutasyonu olanlara göre daha hafif seyretmekteydi. Erken genotipik tanımlama klinik başvuru özelliklerinin tahmin edilmesine ve hastalara en iyi terapötik yaklaşımların uygulanmasına yardımcı olabilir.
β-Thalassemia intermedia is a clinical condition of intermediate gravity between β-thalassemia mi... more β-Thalassemia intermedia is a clinical condition of intermediate gravity between β-thalassemia minor, the asymptomatic carrier, and β-thalassemia major, the transfusion-dependent severe anemia. It is characterized by a significant clinical polymorphism, which is attributable to its genetic heterogeneity. Ineffective erythropoiesis, chronic anemia, and iron overload contribute to the clinical complications of thalassemia intermedia through stepwise pathophysiological mechanisms. These complications, including splenomegaly, extramedullary erythropoiesis, iron accumulation, leg ulcers, thrombophilia, and bone abnormalities can be managed via fetal hemoglobin induction, occasional transfusions, chelation, and in some cases, stem cell transplantation. Given its clinical diversity, thalassemia intermedia patients require tailored approaches to therapy. Here we present an overview and novel approaches to the genetic basis, pathophysiological mechanisms, clinical complications, and optimal ...
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