Aims/hypothesis: The aim of this study was to explore the contribution of genetic factors to the ... more Aims/hypothesis: The aim of this study was to explore the contribution of genetic factors to the emergence of beta-cell-specific humoral autoimmunity. Subjects and methods: We analysed the effect of HLA class II, insulin (INS; -23 HphI variant) and cytotoxic T-lymphocyteassociated protein 4 (CTLA4 [+49 and CT60]) genes on the appearance of beta-cell-specific autoantibodies in a large population-based birth cohort recruited in Finland. Infants carrying increased risk HLA DQB1 genotypes were monitored for the appearance of autoantibodies (islet cell autoantibodies [ICA], insulin autoantibodies [IAA], glutamic acid decarboxylase autoantibodies [GADA] and islet antigen 2 antibodies [IA-2A]). Those who developed beta-cell-specific autoantibodies were studied (n=574, mean follow-up time: 4.9 years; range 0.5-9.3). Results: IAA emerged at a higher rate in children with the -23 HphI AA INS genotype than in those carrying AT or TT variants (hazard ratio 2.1, 95% CI 1.4-2.9, p<0.001). This effect of the INS locus was present in both HLA DQB1 risk groups. The appearance of IAA showed a strong association also with the HLA DRB1*0401 allele (hazard ratio 13.1, 95% CI 1.8-93.4, p<0.001). The development of IA-2A was also somewhat accelerated by the DRB1*0401 variant (p=0.03). Isolated ICA positivity was independent of the HLA and INS genotypes. None of the humoral immune markers showed association with the CTLA4 gene. Conclusions/interpretation: The INS and the DRB1 loci appear to contribute to the pathogenesis of type 1 diabetes by initiating/modifying insulin-specific autoimmunity. The emergence of IAA represents a crucial step in the development of beta cell autoimmunity in young children, in whom the appearance of GADA and IA-2A is linked to IAA.
Type 1 diabetes (T1D) is one of the most prevalent autoimmune diseases among children in Western ... more Type 1 diabetes (T1D) is one of the most prevalent autoimmune diseases among children in Western countries. Earlier metabolomics studies suggest that T1D is preceded by dysregulation of lipid metabolism. Here we used a lipidomics approach to analyze molecular lipids in a prospective series of 428 plasma samples from 40 children who progressed to T1D (PT1D), 40 children who developed at least a single islet autoantibody but did not progress to T1D during the follow-up (P1Ab) and 40 matched controls (CTR). Sphingomyelins were found to be persistently downregulated in PT1D when compared to the P1Ab and CTR groups. Triacylglycerols and phosphatidylcholines were mainly downregulated in PT1D as compared to P1Ab at the age of 3 months. Our study suggests that distinct lipidomic signatures characterize children who progressed to islet autoimmunity or overt T1D, which may be helpful in the identification of at-risk children before the initiation of autoimmunity.
The Journal of Clinical Endocrinology & Metabolism, 2020
Context We set out to characterize the dynamics of islet autoantibodies over the first 15 years o... more Context We set out to characterize the dynamics of islet autoantibodies over the first 15 years of life in children carrying genetic susceptibility to type 1 diabetes (T1D). We also assessed systematically the role of zinc transporter 8 autoantibodies (ZnT8A) in this context. Design HLA-predisposed children (N = 1006, 53.0% boys) recruited from the general population during 1994 to 1997 were observed from birth over a median time of 14.9 years (range, 1.9-15.5 years) for ZnT8A, islet cell (ICA), insulin (IAA), glutamate decarboxylase (GADA), and islet antigen-2 (IA-2A) antibodies, and for T1D. Results By age 15.5 years, 35 (3.5%) children had progressed to T1D. Islet autoimmunity developed in 275 (27.3%) children at a median age of 7.4 years (range, 0.3-15.1 years). The ICA seroconversion rate increased toward puberty, but the biochemically defined autoantibodies peaked at a young age. Before age 2 years, ZnT8A and IAA appeared commonly as the first autoantibody, but in the preschoo...
The Journal of Clinical Endocrinology & Metabolism, 2019
Context Characterization of slow progression to type 1 diabetes (T1D) may reveal novel means for ... more Context Characterization of slow progression to type 1 diabetes (T1D) may reveal novel means for prevention of T1D. Slow progressors might carry natural immunomodulators that delay β-cell destruction and mediate preservation of β-cell function. Objective To identify demographic, genetic, and immunological characteristics of slow progression from seroconversion to clinical T1D. Design HLA-susceptible children (n = 7410) were observed from birth for islet cell antibody (ICA), insulin autoantibody (IAA), glutamic acid decarboxylase (GADA), and islet antigen-2 autoantibodies (IA-2A), and for clinical T1D. Disease progression that lasted ≥7.26 years (slowest) quartile from initial seroconversion to diagnosis was considered slow. Autoantibody and genetic characteristics including 45 non-HLA single nucleotide polymorphisms (SNPs) predisposing to T1D were analyzed. Results By the end of 2015, 1528 children (21%) had tested autoantibody positive and 247 (16%) had progressed to T1D. The media...
Lymphocytes from seronegative and seropositive subjects were stimulated in vitro with herpes simp... more Lymphocytes from seronegative and seropositive subjects were stimulated in vitro with herpes simplex, rubella, mumps and measles viral antigens. Viral antigens were beta-propiolactone inactivated crude material (containing cell-membrane fragments) grown in Vero cells and prepared identically. Lymphocytes from seropositive subjects responded specifically to herpes virus antigen, and most rubella and mumps seropositive subjects responded to the respective antigens. Measles antigen, however, did not stimulate lymphocytes from seropositive or seronegative subjects. The responses of three subjects studied repeatedly over a period of several weeks were reproducible. The results of the study support the usefulness of the blast transformation test as a measure of sensitization to viruses.
Population-based genetic screening for IDDM susceptibility as a source of HLAgenotyped control su... more Population-based genetic screening for IDDM susceptibility as a source of HLAgenotyped control subjects Dear Sir, The problem of finding HLA-matched control subjects for studies of genetics and pathogenesis of insulin-dependent diabetes mellitus (IDDM) has recently been discussed [1, 2]. Because less than 5 % of the background populations have the high-risk genotype DR3-DQ2/DR4-DQ8, collection of reasonable numbers of control samples for DNA and isolation of fresh blood cells for functional studies is difficult. Registers of bone marrow donors have apparent intrinsic problems; e.g., the potential marrow donors are adults and thus inappropriate for several studies of childhood IDDM. Population-based genetic screening for IDDM susceptibility provides an apparently unlimited source of suitable control subjects as a byproduct of the study. The "Diabetes Prediction and Prevention (DIPP)" trial, which was launched in Finland in November 1994, comprises all newborns born at the Turku University Hospital (about 4000 per year). The cord blood samples are typed for those HLA-DQB1 alleles associated with significant risk of or protection from IDDM, DQBI*0201 and *0302 vs DQBl*0301,*0602 and *0603, respectively [3]. The screening will be expanded within a few months to the Oulu University Hospital with a similar number of annual births. The assay developed for screening purposes combines polymerase chain reaction, time-resolved fluorometry and use of lanthanide-labelled, short allele-specific oligonucleotide probes in a solution hybridisation reaction [4]. Children with high genetic IDDM risk are studied for possible markers of beta-cell autoimmunity at regular intervals. Those at imminent risk of disease will be allocated to experimental trials of preventive treatment.
The genes of the Major Histocompatibility Complex (MHC), which plays a fundamental role in the im... more The genes of the Major Histocompatibility Complex (MHC), which plays a fundamental role in the immune system, are some of the most diverse genes in vertebrates and have been connected to mate choice in several species, including humans. While studies suggest a positive relationship between MHC diversity and male facial attractiveness, the connection of MHC diversity to other visual traits and female attractiveness is still unclear. The purpose of this study was to investigate further whether MHC heterozygosity, indicating genetic quality, is associated with visual traits affecting mate preferences in humans. In total 74 Latvian men and 49 women were genotyped for several MHC loci and rated for facial and, in men, also body attractiveness. The results indicate a preference for MHC heterozygous female and male faces. However, the initially positive relationship between MHC heterozygosity and facial attractiveness becomes non-significant in females, when controlling for multiple testin...
AimsType 1 diabetes (T1D) is an autoimmune disease that affects many children worldwide. Genetic ... more AimsType 1 diabetes (T1D) is an autoimmune disease that affects many children worldwide. Genetic factors and environmental triggers play crucial interacting roles in the aetiology. This study aimed to assess the contribution of HLA‐DRB1‐DQA1‐DQB1 alleles, haplotypes, and genotypes to the risk of T1D among Saudis.MethodsA total of 222 children with T1D and 342 controls were genotyped for HLA‐DRB1, ‐DQA1, and ‐DQB1 using reverse sequence‐specific oligonucleotide (rSSO) Lab Type high definition (HD) kits. Alleles, haplotypes, and diplotypes were compared between cases and controls using the SAS statistical package.ResultsDRB1*03:01‐DQA1*05:01‐DQB1*02:01 (32.4%; OR = 3.68; Pc < .0001), DRB1*04:05‐DQA1*03:02‐DQB1*03:02 (6.6%; OR = 6.76; Pc < .0001), DRB1*04:02‐DQA1*03:01‐DQB1*03:02 (6.0%; OR = 3.10; Pc = .0194), DRB1*04:01‐DQA1*03:01‐DQB1*03:02 (3.7%; OR = 4.22; Pc = .0335), and DRB1*04:05‐DQA1*03:02‐DQB1*02:02 (2.7%; OR = 6.31; Pc = .0326) haplotypes were significantly increased i...
BackgroundEchovirus 30 (E-30) is one of the most frequently isolated pathogens in aseptic meningi... more BackgroundEchovirus 30 (E-30) is one of the most frequently isolated pathogens in aseptic meningitis worldwide. To gain access to the central nervous system (CNS), E-30 and immune cells have to cross one of the two main barriers of the CNS, the epithelial blood–cerebrospinal fluid barrier (BCSFB) or the endothelial blood–brain barrier (BBB). In an in vitro model of the BCSFB, it has been shown that E-30 can infect human immortalized brain choroid plexus papilloma (HIBCPP) cells.MethodsIn this study we investigated the migration of different T cell subpopulations, naive and effector T cells, through HIBCPP cells during E-30 infection. Effects of E-30 infection and the migration process were evaluated via immunofluorescence and flow cytometry analysis, as well as transepithelial resistance and dextran flux measurement.ResultsTh1 effector cells and enterovirus-specific effector T cells migrated through HIBCPP cells more efficiently than naive CD4+T cells following E-30 infection of HIB...
Prolonged arthritis associated with Sindbis-related (Pogosta) virus infection SIR, Harley et al. ... more Prolonged arthritis associated with Sindbis-related (Pogosta) virus infection SIR, Harley et al. [1] express concern that we have overinterpreted our results [2]. Their opinion is mainly based on reports of prolonged symptoms caused by Ross River virus. It may have escaped the attention of Harley et al. that the method used in our study was not at all based on mailed questionnaires. All our patients were personally interviewed and examined by a physician, and their earlier hospital records were analysed. Suspected arthritis was further verified by X-ray and ultrasonography. There was no significant participation bias, because 26 out of 30 patients accepted the invitation. Harley et al. worry that suspicion of Pogosta disease leads to inappropriate and superfluous treatment. This is hardly the case, as there is no specific treatment of Pogosta (Sindbis) virus infection. Musculoskeletal symptoms, whether acute or chronic, often require management which is in most cases based on anti-inflammatory agents.
Acta pathologica et microbiologica Scandinavica. Section C, Immunology, 1979
Lymphocytes from seronegative and seropositive subjects were stimulated in vitro with herpes simp... more Lymphocytes from seronegative and seropositive subjects were stimulated in vitro with herpes simplex, rubella, mumps and measles viral antigens. Viral antigens were beta-propiolactone inactivated crude material (containing cell-membrane fragments) grown in Vero cells and prepared identically. Lymphocytes from seropositive subjects responded specifically to herpes virus antigen, and most rubella and mumps seropositive subjects responded to the respective antigens. Measles antigen, however, did not stimulate lymphocytes from seropositive or seronegative subjects. The responses of three subjects studied repeatedly over a period of several weeks were reproducible. The results of the study support the usefulness of the blast transformation test as a measure of sensitization to viruses.
Dietary wheat gluten has been associated with the risk of diabetes in animal models of human insu... more Dietary wheat gluten has been associated with the risk of diabetes in animal models of human insulin‐dependent diabetes mellitus (IDDM). To evaluate the role of wheat gluten as a T cell antigen in human IDDM, we studied the cell‐mediated immune response to wheat gluten in patients with IDDM and in control subjects. The cellular response to gluten was measured by the peripheral blood mononuclear cell (PBMC) proliferation test, and the results were expressed as a stimulation index (SI). We observed an enhanced cellular immune response to gluten (SI ≥ 3) in seven of 29 patients with newly diagnosed IDDM (24.1%), in six of 39 patients with a longer duration of IDDM (15.4%), and in two of 37 non‐diabetic controls (5.4%). Reactivity of T cells to gluten was associated with IDDM at diagnosis (P = 0.03), whereas patients with longer duration of IDDM did not differ from controls (P = 0.16). Responses of T cells to gluten were low in general: the median SI (range) was 2.0 (1–8.6) in patients ...
Summary The infection of human peripheral blood leukocytes by varicella-zoster virus (VZV) was st... more Summary The infection of human peripheral blood leukocytes by varicella-zoster virus (VZV) was studied using an infectious center assay, indirect immunofluorescence and electron microscopy. Subsets of freshly isolated leukocytes were prepared, including granulocytes, mononuclear cells from Ficoll-Hypaque gradients, lymphocytes, and glass-adherent monocytes. When each of these populations was inoculated with VZV (MOI = 0.1), there was no evidence of effective
The study aimed to further characterise HLA encoded risk factors of type 1 diabetes (T1D) in Braz... more The study aimed to further characterise HLA encoded risk factors of type 1 diabetes (T1D) in Brazilian population and test the capability of a low resolution full-house DR-DQ typing method to find subjects at diabetes risk. Insulin and CTLA-4 gene polymorphisms were also analysed. The method is based on an initial DQB1 typing supplemented by DQA1 and DR4 subtyping when informative. Increased frequencies of both (DR3)-DQA1*05-DQB1*02 and DRB1*04-DQA1*03-DQB1*0302 haplotypes were detected among patients. DRB1*0401, *0402, *0404 and *0405 alleles were all common in DQB1*0302 haplotypes and associated with T1D. (DRB1*11/12/1303)-DQA1*05-DQB1*0301, (DRB1*01/10)-DQB1*0501, (DRB1*15)-DQB1*0602 and (DRB1*1301)-*0603 haplotypes were significantly decreased among patients. Genotypes with two risk haplotypes or a combination of a susceptibility associated and a neutral haplotype were found in 78 of 126 (61.9%) T1D patients compared to 8 of 75 (10.7%) control subjects (P< 0.0001). Insulin ge...
European Journal of Clinical Nutrition, Jan 13, 2016
BACKGROUND/OBJECTIVES: Diet during pregnancy and lactation may have a role in the development of ... more BACKGROUND/OBJECTIVES: Diet during pregnancy and lactation may have a role in the development of allergic diseases. There are few human studies on the topic, especially focusing on food allergies. We sought to study the associations between maternal diet during pregnancy and lactation and cow's milk allergy (CMA) in offspring. SUBJECTS/METHODS: A population-based birth cohort with human leukocyte antigen-conferred susceptibility to type 1 diabetes was recruited in Finland between 1997 and 2004 (n = 6288). Maternal diet during pregnancy and lactation was assessed by a validated, 181item semi-quantitative food frequency questionnaire. Register-based information on diagnosed CMA was obtained from the Social Insurance Institution and completed with parental reports. The associations between maternal food consumption and CMA were assessed using logistic regression, comparing the highest and the lowest quarters to the middle half of consumption. RESULTS: Consumption of milk products in the highest quarter during pregnancy was associated with a lower risk of CMA in offspring (odds ratio (OR) 0.56, 95% confidence interval (CI) 0.37-0.86; P o 0.01). When stratified by maternal allergic rhinitis and asthma, there was evidence of an inverse association between high use of milk products and CMA in offspring of non-allergic mothers (OR 0.30, 95% CI 0.13-0.69, P o0.001). Cord blood IgA correlated positively with the consumption of milk products during pregnancy, indicating exposure to CMA and activation of antigen-specific immunity in the infant during pregnancy. CONCLUSIONS: High maternal consumption of milk products during pregnancy may protect children from developing CMA, especially in offspring of non-allergic mothers.
Aims/hypothesis: The aim of this study was to explore the contribution of genetic factors to the ... more Aims/hypothesis: The aim of this study was to explore the contribution of genetic factors to the emergence of beta-cell-specific humoral autoimmunity. Subjects and methods: We analysed the effect of HLA class II, insulin (INS; -23 HphI variant) and cytotoxic T-lymphocyteassociated protein 4 (CTLA4 [+49 and CT60]) genes on the appearance of beta-cell-specific autoantibodies in a large population-based birth cohort recruited in Finland. Infants carrying increased risk HLA DQB1 genotypes were monitored for the appearance of autoantibodies (islet cell autoantibodies [ICA], insulin autoantibodies [IAA], glutamic acid decarboxylase autoantibodies [GADA] and islet antigen 2 antibodies [IA-2A]). Those who developed beta-cell-specific autoantibodies were studied (n=574, mean follow-up time: 4.9 years; range 0.5-9.3). Results: IAA emerged at a higher rate in children with the -23 HphI AA INS genotype than in those carrying AT or TT variants (hazard ratio 2.1, 95% CI 1.4-2.9, p<0.001). This effect of the INS locus was present in both HLA DQB1 risk groups. The appearance of IAA showed a strong association also with the HLA DRB1*0401 allele (hazard ratio 13.1, 95% CI 1.8-93.4, p<0.001). The development of IA-2A was also somewhat accelerated by the DRB1*0401 variant (p=0.03). Isolated ICA positivity was independent of the HLA and INS genotypes. None of the humoral immune markers showed association with the CTLA4 gene. Conclusions/interpretation: The INS and the DRB1 loci appear to contribute to the pathogenesis of type 1 diabetes by initiating/modifying insulin-specific autoimmunity. The emergence of IAA represents a crucial step in the development of beta cell autoimmunity in young children, in whom the appearance of GADA and IA-2A is linked to IAA.
Type 1 diabetes (T1D) is one of the most prevalent autoimmune diseases among children in Western ... more Type 1 diabetes (T1D) is one of the most prevalent autoimmune diseases among children in Western countries. Earlier metabolomics studies suggest that T1D is preceded by dysregulation of lipid metabolism. Here we used a lipidomics approach to analyze molecular lipids in a prospective series of 428 plasma samples from 40 children who progressed to T1D (PT1D), 40 children who developed at least a single islet autoantibody but did not progress to T1D during the follow-up (P1Ab) and 40 matched controls (CTR). Sphingomyelins were found to be persistently downregulated in PT1D when compared to the P1Ab and CTR groups. Triacylglycerols and phosphatidylcholines were mainly downregulated in PT1D as compared to P1Ab at the age of 3 months. Our study suggests that distinct lipidomic signatures characterize children who progressed to islet autoimmunity or overt T1D, which may be helpful in the identification of at-risk children before the initiation of autoimmunity.
The Journal of Clinical Endocrinology & Metabolism, 2020
Context We set out to characterize the dynamics of islet autoantibodies over the first 15 years o... more Context We set out to characterize the dynamics of islet autoantibodies over the first 15 years of life in children carrying genetic susceptibility to type 1 diabetes (T1D). We also assessed systematically the role of zinc transporter 8 autoantibodies (ZnT8A) in this context. Design HLA-predisposed children (N = 1006, 53.0% boys) recruited from the general population during 1994 to 1997 were observed from birth over a median time of 14.9 years (range, 1.9-15.5 years) for ZnT8A, islet cell (ICA), insulin (IAA), glutamate decarboxylase (GADA), and islet antigen-2 (IA-2A) antibodies, and for T1D. Results By age 15.5 years, 35 (3.5%) children had progressed to T1D. Islet autoimmunity developed in 275 (27.3%) children at a median age of 7.4 years (range, 0.3-15.1 years). The ICA seroconversion rate increased toward puberty, but the biochemically defined autoantibodies peaked at a young age. Before age 2 years, ZnT8A and IAA appeared commonly as the first autoantibody, but in the preschoo...
The Journal of Clinical Endocrinology & Metabolism, 2019
Context Characterization of slow progression to type 1 diabetes (T1D) may reveal novel means for ... more Context Characterization of slow progression to type 1 diabetes (T1D) may reveal novel means for prevention of T1D. Slow progressors might carry natural immunomodulators that delay β-cell destruction and mediate preservation of β-cell function. Objective To identify demographic, genetic, and immunological characteristics of slow progression from seroconversion to clinical T1D. Design HLA-susceptible children (n = 7410) were observed from birth for islet cell antibody (ICA), insulin autoantibody (IAA), glutamic acid decarboxylase (GADA), and islet antigen-2 autoantibodies (IA-2A), and for clinical T1D. Disease progression that lasted ≥7.26 years (slowest) quartile from initial seroconversion to diagnosis was considered slow. Autoantibody and genetic characteristics including 45 non-HLA single nucleotide polymorphisms (SNPs) predisposing to T1D were analyzed. Results By the end of 2015, 1528 children (21%) had tested autoantibody positive and 247 (16%) had progressed to T1D. The media...
Lymphocytes from seronegative and seropositive subjects were stimulated in vitro with herpes simp... more Lymphocytes from seronegative and seropositive subjects were stimulated in vitro with herpes simplex, rubella, mumps and measles viral antigens. Viral antigens were beta-propiolactone inactivated crude material (containing cell-membrane fragments) grown in Vero cells and prepared identically. Lymphocytes from seropositive subjects responded specifically to herpes virus antigen, and most rubella and mumps seropositive subjects responded to the respective antigens. Measles antigen, however, did not stimulate lymphocytes from seropositive or seronegative subjects. The responses of three subjects studied repeatedly over a period of several weeks were reproducible. The results of the study support the usefulness of the blast transformation test as a measure of sensitization to viruses.
Population-based genetic screening for IDDM susceptibility as a source of HLAgenotyped control su... more Population-based genetic screening for IDDM susceptibility as a source of HLAgenotyped control subjects Dear Sir, The problem of finding HLA-matched control subjects for studies of genetics and pathogenesis of insulin-dependent diabetes mellitus (IDDM) has recently been discussed [1, 2]. Because less than 5 % of the background populations have the high-risk genotype DR3-DQ2/DR4-DQ8, collection of reasonable numbers of control samples for DNA and isolation of fresh blood cells for functional studies is difficult. Registers of bone marrow donors have apparent intrinsic problems; e.g., the potential marrow donors are adults and thus inappropriate for several studies of childhood IDDM. Population-based genetic screening for IDDM susceptibility provides an apparently unlimited source of suitable control subjects as a byproduct of the study. The "Diabetes Prediction and Prevention (DIPP)" trial, which was launched in Finland in November 1994, comprises all newborns born at the Turku University Hospital (about 4000 per year). The cord blood samples are typed for those HLA-DQB1 alleles associated with significant risk of or protection from IDDM, DQBI*0201 and *0302 vs DQBl*0301,*0602 and *0603, respectively [3]. The screening will be expanded within a few months to the Oulu University Hospital with a similar number of annual births. The assay developed for screening purposes combines polymerase chain reaction, time-resolved fluorometry and use of lanthanide-labelled, short allele-specific oligonucleotide probes in a solution hybridisation reaction [4]. Children with high genetic IDDM risk are studied for possible markers of beta-cell autoimmunity at regular intervals. Those at imminent risk of disease will be allocated to experimental trials of preventive treatment.
The genes of the Major Histocompatibility Complex (MHC), which plays a fundamental role in the im... more The genes of the Major Histocompatibility Complex (MHC), which plays a fundamental role in the immune system, are some of the most diverse genes in vertebrates and have been connected to mate choice in several species, including humans. While studies suggest a positive relationship between MHC diversity and male facial attractiveness, the connection of MHC diversity to other visual traits and female attractiveness is still unclear. The purpose of this study was to investigate further whether MHC heterozygosity, indicating genetic quality, is associated with visual traits affecting mate preferences in humans. In total 74 Latvian men and 49 women were genotyped for several MHC loci and rated for facial and, in men, also body attractiveness. The results indicate a preference for MHC heterozygous female and male faces. However, the initially positive relationship between MHC heterozygosity and facial attractiveness becomes non-significant in females, when controlling for multiple testin...
AimsType 1 diabetes (T1D) is an autoimmune disease that affects many children worldwide. Genetic ... more AimsType 1 diabetes (T1D) is an autoimmune disease that affects many children worldwide. Genetic factors and environmental triggers play crucial interacting roles in the aetiology. This study aimed to assess the contribution of HLA‐DRB1‐DQA1‐DQB1 alleles, haplotypes, and genotypes to the risk of T1D among Saudis.MethodsA total of 222 children with T1D and 342 controls were genotyped for HLA‐DRB1, ‐DQA1, and ‐DQB1 using reverse sequence‐specific oligonucleotide (rSSO) Lab Type high definition (HD) kits. Alleles, haplotypes, and diplotypes were compared between cases and controls using the SAS statistical package.ResultsDRB1*03:01‐DQA1*05:01‐DQB1*02:01 (32.4%; OR = 3.68; Pc < .0001), DRB1*04:05‐DQA1*03:02‐DQB1*03:02 (6.6%; OR = 6.76; Pc < .0001), DRB1*04:02‐DQA1*03:01‐DQB1*03:02 (6.0%; OR = 3.10; Pc = .0194), DRB1*04:01‐DQA1*03:01‐DQB1*03:02 (3.7%; OR = 4.22; Pc = .0335), and DRB1*04:05‐DQA1*03:02‐DQB1*02:02 (2.7%; OR = 6.31; Pc = .0326) haplotypes were significantly increased i...
BackgroundEchovirus 30 (E-30) is one of the most frequently isolated pathogens in aseptic meningi... more BackgroundEchovirus 30 (E-30) is one of the most frequently isolated pathogens in aseptic meningitis worldwide. To gain access to the central nervous system (CNS), E-30 and immune cells have to cross one of the two main barriers of the CNS, the epithelial blood–cerebrospinal fluid barrier (BCSFB) or the endothelial blood–brain barrier (BBB). In an in vitro model of the BCSFB, it has been shown that E-30 can infect human immortalized brain choroid plexus papilloma (HIBCPP) cells.MethodsIn this study we investigated the migration of different T cell subpopulations, naive and effector T cells, through HIBCPP cells during E-30 infection. Effects of E-30 infection and the migration process were evaluated via immunofluorescence and flow cytometry analysis, as well as transepithelial resistance and dextran flux measurement.ResultsTh1 effector cells and enterovirus-specific effector T cells migrated through HIBCPP cells more efficiently than naive CD4+T cells following E-30 infection of HIB...
Prolonged arthritis associated with Sindbis-related (Pogosta) virus infection SIR, Harley et al. ... more Prolonged arthritis associated with Sindbis-related (Pogosta) virus infection SIR, Harley et al. [1] express concern that we have overinterpreted our results [2]. Their opinion is mainly based on reports of prolonged symptoms caused by Ross River virus. It may have escaped the attention of Harley et al. that the method used in our study was not at all based on mailed questionnaires. All our patients were personally interviewed and examined by a physician, and their earlier hospital records were analysed. Suspected arthritis was further verified by X-ray and ultrasonography. There was no significant participation bias, because 26 out of 30 patients accepted the invitation. Harley et al. worry that suspicion of Pogosta disease leads to inappropriate and superfluous treatment. This is hardly the case, as there is no specific treatment of Pogosta (Sindbis) virus infection. Musculoskeletal symptoms, whether acute or chronic, often require management which is in most cases based on anti-inflammatory agents.
Acta pathologica et microbiologica Scandinavica. Section C, Immunology, 1979
Lymphocytes from seronegative and seropositive subjects were stimulated in vitro with herpes simp... more Lymphocytes from seronegative and seropositive subjects were stimulated in vitro with herpes simplex, rubella, mumps and measles viral antigens. Viral antigens were beta-propiolactone inactivated crude material (containing cell-membrane fragments) grown in Vero cells and prepared identically. Lymphocytes from seropositive subjects responded specifically to herpes virus antigen, and most rubella and mumps seropositive subjects responded to the respective antigens. Measles antigen, however, did not stimulate lymphocytes from seropositive or seronegative subjects. The responses of three subjects studied repeatedly over a period of several weeks were reproducible. The results of the study support the usefulness of the blast transformation test as a measure of sensitization to viruses.
Dietary wheat gluten has been associated with the risk of diabetes in animal models of human insu... more Dietary wheat gluten has been associated with the risk of diabetes in animal models of human insulin‐dependent diabetes mellitus (IDDM). To evaluate the role of wheat gluten as a T cell antigen in human IDDM, we studied the cell‐mediated immune response to wheat gluten in patients with IDDM and in control subjects. The cellular response to gluten was measured by the peripheral blood mononuclear cell (PBMC) proliferation test, and the results were expressed as a stimulation index (SI). We observed an enhanced cellular immune response to gluten (SI ≥ 3) in seven of 29 patients with newly diagnosed IDDM (24.1%), in six of 39 patients with a longer duration of IDDM (15.4%), and in two of 37 non‐diabetic controls (5.4%). Reactivity of T cells to gluten was associated with IDDM at diagnosis (P = 0.03), whereas patients with longer duration of IDDM did not differ from controls (P = 0.16). Responses of T cells to gluten were low in general: the median SI (range) was 2.0 (1–8.6) in patients ...
Summary The infection of human peripheral blood leukocytes by varicella-zoster virus (VZV) was st... more Summary The infection of human peripheral blood leukocytes by varicella-zoster virus (VZV) was studied using an infectious center assay, indirect immunofluorescence and electron microscopy. Subsets of freshly isolated leukocytes were prepared, including granulocytes, mononuclear cells from Ficoll-Hypaque gradients, lymphocytes, and glass-adherent monocytes. When each of these populations was inoculated with VZV (MOI = 0.1), there was no evidence of effective
The study aimed to further characterise HLA encoded risk factors of type 1 diabetes (T1D) in Braz... more The study aimed to further characterise HLA encoded risk factors of type 1 diabetes (T1D) in Brazilian population and test the capability of a low resolution full-house DR-DQ typing method to find subjects at diabetes risk. Insulin and CTLA-4 gene polymorphisms were also analysed. The method is based on an initial DQB1 typing supplemented by DQA1 and DR4 subtyping when informative. Increased frequencies of both (DR3)-DQA1*05-DQB1*02 and DRB1*04-DQA1*03-DQB1*0302 haplotypes were detected among patients. DRB1*0401, *0402, *0404 and *0405 alleles were all common in DQB1*0302 haplotypes and associated with T1D. (DRB1*11/12/1303)-DQA1*05-DQB1*0301, (DRB1*01/10)-DQB1*0501, (DRB1*15)-DQB1*0602 and (DRB1*1301)-*0603 haplotypes were significantly decreased among patients. Genotypes with two risk haplotypes or a combination of a susceptibility associated and a neutral haplotype were found in 78 of 126 (61.9%) T1D patients compared to 8 of 75 (10.7%) control subjects (P< 0.0001). Insulin ge...
European Journal of Clinical Nutrition, Jan 13, 2016
BACKGROUND/OBJECTIVES: Diet during pregnancy and lactation may have a role in the development of ... more BACKGROUND/OBJECTIVES: Diet during pregnancy and lactation may have a role in the development of allergic diseases. There are few human studies on the topic, especially focusing on food allergies. We sought to study the associations between maternal diet during pregnancy and lactation and cow's milk allergy (CMA) in offspring. SUBJECTS/METHODS: A population-based birth cohort with human leukocyte antigen-conferred susceptibility to type 1 diabetes was recruited in Finland between 1997 and 2004 (n = 6288). Maternal diet during pregnancy and lactation was assessed by a validated, 181item semi-quantitative food frequency questionnaire. Register-based information on diagnosed CMA was obtained from the Social Insurance Institution and completed with parental reports. The associations between maternal food consumption and CMA were assessed using logistic regression, comparing the highest and the lowest quarters to the middle half of consumption. RESULTS: Consumption of milk products in the highest quarter during pregnancy was associated with a lower risk of CMA in offspring (odds ratio (OR) 0.56, 95% confidence interval (CI) 0.37-0.86; P o 0.01). When stratified by maternal allergic rhinitis and asthma, there was evidence of an inverse association between high use of milk products and CMA in offspring of non-allergic mothers (OR 0.30, 95% CI 0.13-0.69, P o0.001). Cord blood IgA correlated positively with the consumption of milk products during pregnancy, indicating exposure to CMA and activation of antigen-specific immunity in the infant during pregnancy. CONCLUSIONS: High maternal consumption of milk products during pregnancy may protect children from developing CMA, especially in offspring of non-allergic mothers.
Uploads
Papers by Jorma Ilonen