Frequency Of DRB1 Research Articles

Potential contribution of gut microbiota in the development of autoantibodies in T1D children carrying HLA-DRB1/DQB1 risk alleles: an experimental and in silico analysis.

This study aimed to investigate the prevalence of insulin autoantibody (IAA), glutamic acid decarboxylase antibody (GADA), and insulinoma-associated antigen-2 antibody (IA-2A) in type 1 diabetes (T1D) children based on the presence of predisposing HLA-II alleles. Additionally, to assess the sequence homology between autoantigens of islet cells and selected proteins derived from gut bacteria in terms of their binding capacities to HLA risk alleles, HLA-DRB1/DQB1 alleles were determined by PCR-SSOP in 111 T1D children (probands) along with 222 parents and 133 siblings. Autoantibodies were measured by ELISA, and in silico analysis was run as follows: protein extraction, homology and epitope prediction, peptide alignment, and HLA-peptide docking. Higher significant frequencies of DRB1*03:01, DQB1*02:01, and DQB1*03:02 alleles and DRB1*03:01 ~ DQB1*02:01 haplotype and lower frequencies of DRB1*11:01, DRB1*14:01, and DQB1*03:01 alleles were found in probands compared to parents and siblings. DRB1*11:01 ~ DQB1*03:01, DRB1*14:01 ~ DQB1*05:03, and DRB1*15:01-DQB1*06:02 haplotypes were significantly less frequent in the probands compared to parents. Out of 111 probands, 21 were seronegative, 90 tested positive for one autoantibody, and 15 showed the concurrent presence of three autoantibodies. Logistic regression analysis revealed that DRB1*04 ~ DQB1*03:02 haplotype was associated with the induction of GADA and IA-2A, while DRB1*11:01 ~ DQB1*03:01 was associated with seronegativity. Epitopes derived from GAD and gut bacteria showed strong binding capacities to HLA risk alleles. Due to the sequence similarities between gut bacteria-derived proteins and islet cell autoantigens and their potential for binding to HLA risk alleles, dysbiosis of gut microbiota can be considered another risk factor for the development of T1D, especially in genetically susceptible individuals.

Immunological markers of rheumatoid arthritis in the Moroccan population

Aim: few studies exist on HLA-DRB1 alleles and their association with RA in North Africa. We aimed to provide an evaluation of the distribution of the HLA-DRB1* and -DQB1* genes in Moroccan patients with early RA. Additionally, we sought to analyze the relationship between HLA molecules and the production of rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP) in these patients. Methods: 65 patients with rheumatoid arthritis benefited from HLA class II typing (DRB1* and DQB1*) and testing for anti-CCP and RF antibodies. The frequency of HLA alleles was compared to that of 180 healthy controls. Logistic regression analysis was used to investigate the association of HLA-DR and -DQ molecules in the different subgroups according to anti-CCP and RF status. Results: The frequency of HLA-DRB1*04 and *11 alleles is increased in patients compared to controls (OR = 1.9; 95% CI (1.06-3.30), P=0.029; OR=2, 95% CI (1-3.83, P=0.047, respectively). 56 patients (86.1%) were RF positive, and 67.7% were anti-CCP positive. A significant increase in the frequency of DRB1*04 alleles was also noted in seropositive patients. Conclusion: Our results suggest the predisposition of the HLA-DRB1*04 allele and the seropositive status of patients with RA. This could be useful in predicting the evolution of RA and establishing a diagnosis in some patients at an early stage of disease use.

Association Between HLA-DRB1 Alleles and Graves' Disease in Asian Populations: A Meta-Analysis.

Graves' disease (GD) is an autoimmune disease that primarily affects the thyroid gland. It is the most common cause of hyperthyroidism. Genetic studies have shown that human leukocyte antigen (HLA) plays an important role in the development of GD. In this article, we performed a meta-analysis determined to evaluate the relationship between HLA-DRB1 alleles and GD. This meta-analysis included 9 studies (3582 cases in the case group and 23070 cases in the control group) and 27 alleles was performed. The combined results showed that, compared with the control group, GD patients have a significant increase in the frequency of DRB1*1403 (OR=2.50, 95% CI=1.78-3.51, pc<0.0001) and have a significant decrease in frequencies of DRB1* 0101 (OR=0.45, 95% CI=0.34-0.59, pc<0.0001) and DRB1*0701 (OR=0.44, 95% CI=0.35-0.55, pc<0.0001). The meta-analysis indicated that, in Asian populations, DRB1*1403 is a risk allele for GD, and DRB1*0101 and DRB1*0701 are protective against the occurrence of GD. We surprisingly discovered that the susceptibility alleles for GD in Asian populations are completely different from Caucasians and the protective alleles for GD in Asians are quite similar to those of Caucasians. The results of our study may provide new opportunities for gene-targeted therapy for GD in Asian populations.

Association of Hematological and Biochemical Parameters and HLA-DRB1 Alleles With Anti-cyclic Citrullinated Peptide Autoantibodies in Sudanese Rheumatic Patients.

Introduction Anti-citrullinated protein/peptide antibodies (ACPA) are crucial for the diagnosis and prognosis of rheumatoid arthritis (RA) and are associated with class II HLA-DRB1 alleles. The study's goal was to determine howDRB1alleles and hematological and biochemical parameters affect ACPA production in RA patients from Sudan. Methods The study analyzed the hematological and biochemical parameters and the frequency ofHLA-DRB1alleles in 120 RA patients and 100 controls. Automated analyzers, ELISA, the latex agglutination test, and the Westergren method were utilized for hematological and biochemical testing. HLA class II alleles were genotyped using polymerase chain reaction-sequence-specific primers (PCR-SSP). The student's t-test and the chi-square (Χ2) test were employed to identify significant alterations between the examined parameters and allele frequencies. Results A total of 51.7% of 120 RA patients tested positive for ACPA (ACPA+). Among those patients, theDRB1*04and*10alleles were significantly more prevalent (22.2% vs. 8.9%, P = 0.048 and 23.8% vs. 8.9%, P = 0.030, respectively). RA patients had significantly higher counts of platelet count test (PLT; P= 0.011), lymphocytes (LY; P =0.000), neutrophils (NE; P= 0.025), monocytes (MO; P= 0.000), eosinophils (EO; P= 0.000), neutrophil-to-lymphocyte ratio (NLR; P= 0.006), C-reactive protein (CRP; P= 0.000), and erythrocyte sedimentation rate (ESR; P= 0.000) than controls. Patients also showed low counts of red blood cells (RBC; P= 0.003), hemoglobin (Hb; P= 0.024), mean platelet volume (MPV; P= 0.000), and basophils (BA; P= 0.048). ACPA+RA patients had elevated white blood cells (WBC; P= 0.046), PLT (P= 0.029), and low mean corpuscular hemoglobin concentration (MCHC; P =0.022). The hematological and biochemical parameters of ACPA+RA patients with theDRB1*04or*10alleles did not differ significantly. Conclusions We found significant differences in hematological and biochemical parameters between RA patients and controls that had nothing to do with ACPA positivity or the frequency ofDRB1*04or*10alleles.

Influence of HLA-A, [sbnd]B, and -DRB1 genes and panel-reactive antibodies on the waitlist time for kidney transplantation in the state of Sao Paulo-Brazil

BackgroundBrazil ranks second in the absolute number of transplants. However, the supply remains insufficient to meet the demands, resulting in a lengthy waitlist. This study aimed to analyze whether the frequency of human leukocyte antigen (HLA) and the value of calculated panel reactive antibody (cPRA) would influence the waiting time for kidney transplantation. MethodsThe HLA-A, B, and -DRB1 frequencies and the cPRA value were analyzed in 11,186 kidney transplant candidates included in the waitlist from 2006 to 2016. ResultsThe most frequent alleles were HLA-A*02, HLA-B*35, and HLA-DRB1*13. The overall mean length of stay on the list was 986 ± 1001 days. The mean waiting time for the three most frequent alleles of the HLA-A and B loci showed no significant difference when compared with the least frequent alleles; however, for the HLA-DRB1 locus, the most frequent alleles showed a shorter waiting time. In the association between HLA and PRA, the average length of stay on the list increased according to the candidate's degree of sensitization, regardless of the analyzed HLA frequency. ConclusionThe length of stay on the waitlist is influenced by the frequency of the HLA alleles of the DRB1 locus and the degree of sensitization.

Association of HLA class I and II genes with cervical cancer susceptibility in a Han Chinese population.

Cervical cancer (CC) is one of the leading causes of cancer-related death in females worldwide. Genome-wide association studies (GWASs) have identified CC-related susceptibility loci in HLA regions. To investigate the associations between HLA genes and cervical intraepithelial neoplasia (CIN) or cervical cancer (CC), six loci of HLA class I (HLA-A, -B, and -C) and II (HLA-DRB1, -DPB1, and -DQB1) were selected for genotyping, and the associations between these alleles or their haplotypes with CIN or CC risk or protection from disease were evaluated. In total, 2193 participants, including 909 healthy individuals in the control group, 769 patients with CC, and 515 patients with CIN2+ (CIN II and III), were enrolled in the current study. HLA genes were genotyped using the NGSgo Illumina MiSeq workflow, and the associations between these loci and CIN2+ or CC at the allele and haplotype levels were analyzed. The allele frequencies of HLA-A*33:03, B*58:01, C*03:02, DPB1*05:01, and DRB1*12:01 were lower in both the CC and CIN2+ groups than in the control group, whereas those of B*55:02, C*04:03, and DPB1*03:01 were higher in the CC group than in the control group. In the histologic CC type analysis, the differences in the frequencies of these alleles in squamous cell carcinoma (SCC) of the cervix and stage I CC showed a consistent trend. In the haplotype analysis, the frequency of A*33:03-C*03:02-B*58:01 was lower in the CC and CIN2+ groups than in the control group, and that of A*24:02-C*04:03-B*15:25 was higher in the CC group than in both the control and CIN2+ groups. These three different haplotype frequencies were also identified in the FIGO CC stage analysis. In addition, in human papilloma virus (HPV) genotype analyses, the frequencies of HLA-C*03:02 and DPB1*05:01 were significantly lower in the CC and CIN2+ groups than in the control group, and in SCC subgroup, the frequencies of HLA-DQB1*04:01 and DRB1*04:05 were higher in the HPV other genotype infection group than in the HPV16 infection group. In both HPV16 single infection and coinfection with other HPVs, the frequency of haplotype A*33:03-C*03:02-B*58:01 was lower in both CC and CIN2+ than in the control group, while the frequencies of A*11:01-C*14:02-B*51:01 and A*24:02-C*03:04-B*13:01 were higher in the CIN2+ than in CC and the control group. In the HPV16 and other HPV infection comparisons, the frequencies of DRB1*04:05-DQB1*04:01-DPB1*02:01 and DRB1*11:01-DQB1*03:01-DPB1*05:01 were lower in the HPV16 infection group than in the other HPV infection group. Our results suggest that the HLA class I and II genes may affect the risk of CIN and CC as well as the histologic CC types and FIGO stages of CC in the Han Chinese population. In addition, HLA genes were associated with HPV16 infection at both the allelic and haplotype levels.

Increased Frequency of the HLA-DRB1*04:04-DQA1*03-DQB1*03:02 Haplotype Among HLA-DQB1*06:02-Positive Children With Type 1 Diabetes.

HLA DR-DQ haplotypes largely define genetic susceptibility to type 1 diabetes (T1D). The DQB1*06:02 positive haplotype (DR15-DQ602) common in subjects of European ancestry is very rare among children with T1D. Among 4490 children with T1D in the Finnish Pediatric Diabetes Register 57 (1.3%) cases with DQB1*06:02 were identified in comparison to 26.1% of affected family-based association controls. There was no difference between DQB1*06:02 positive and negative children with T1D regarding sex, age, islet autoantibody distribution or autoantibody levels, but significant differences were seen in the frequency of the second class II HLA haplotypes. The most prevalent haplotype present with DQB1*06:02 was DRB1*04:04-DQA1*03-DQB1*03:02 which was found in 27 of 57 (47.4%) children compared to only 797/4433 (18.0%) among DQB1*06:02 negative cases (P<0.001, Chi-square test). The other common risk associated haplotypes, the DRB1*04:01-DQA1*03-DQB1*03:02 and (DR3)-DQA1*05-DQB1*02 were less prevalent in DQB1*06:02 positive than DQB1*06:02 negative children (P<0.001). HLA-B allele frequencies did not differ between DQB1*06:02 haplotypes in children with T1D and controls and neither in DRB1*04:04-DQA1*03-DQB1*03:02 haplotypes of DQB1*06:02 positive and negative T1D children. The increased frequency of DRB1*04:04 allele among DQB1*06:02 positive cases may indicate preferential ability of the DR404 molecule to present islet antigen epitopes despite of the competition by DQ602.

Associations of HLA Polymorphisms with Chronic Kidney Disease in Japanese Rheumatoid Arthritis Patients.

The prevalence of chronic kidney disease (CKD) was reported to be higher in rheumatoid arthritis (RA) patients than in normal healthy individuals. Human leukocyte antigen (HLA) was associated with RA or CKD. Few studies on the association of HLA with CKD in RA have been reported. Here, we investigated the association of HLA polymorphisms with CKD in Japanese RA patients. HLA-DRB1 genotyping was conducted in 351 Japanese RA patients with CKD (estimated glomerular filtration rate [eGFR] lower than 60 [mL/min/1.73 m2]) and 959 without CKD (eGFR equal to or higher than 60 [mL/min/1.73 m2]). Associations of allele carrier frequencies of DRB1 with CKD were examined in the RA patients. There was an association of DRB1*13:02 with CKD in RA, but this did not achieve statistical significance (p = 0.0265, odds ratio [OR] 1.70, pc = 0.7412, 95% confidence interval [CI] 1.09-2.64). The DR6 serological group was associated with CKD in RA (p = 0.0008, OR 1.65, 95% CI 1.24-2.20). A gene-dosage effect of DR6 was not detected. Logistic regression analysis showed that the association of DR6 with CKD in RA was independent of clinical characteristics. The present study first revealed the independent predisposing association of DR6 with CKD in Japanese RA patients, although DR6 is known to be protective against RA. Our data suggest direct or indirect roles of HLA for the development of CKD in RA, but the mechanisms are not clear.

The Protective Effect of HLA-DRB1 and HLA-DQB1 Alleles to ACPA-Positive and RF-Positive RA in Albanian Population

BACKGOUND: The prevalence of rheumatoid arthritis (RA) and its specific autoantibodies varies in different populations. This variability depends on the genetic polymorphism of the immune response genes among which the HLA system plays a major role. AIM: We conducted a preliminary study of the distribution of HLA-DRB1 and HLA-DQB1 first field level alleles in a sample of 100 Albanian patients with RA. METHODS: In this context, we studied the HLA-DRB1 and HLA-DQB1 first-level allele frequencies in 100 Albanian patients with RA and considering their rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA) serologic subgroups. We compared them with the respective frequencies in a population of 191 Albanian individuals without known pathology. RESULTS: No differences were found between the controls and the RA patient group, but three statistically significant differences were found: an increase in DRB1*04 among ACPA-positive, RF-positive and ACPA-positive/RF-positive patients, a significant decrease in DRB1*11 among ACPA-positive/RF-positive, and also a decrease in DRB1*13 among RF-positive patient subgroups. The frequencies of DRB1 allotypes in ACPA+ and RF+ patients compared to their counterpart ACPA− and RF−patient subgroups showed the predisposing effect of HLA-DRB1*04 for ACPA and RF seropositivity (p, respectively, 0.0008 and 0.0017) and the protective role of HLA-DRB1*11 for ACPA and RF positivity (p, respectively, 0.007 and 0.02). The same protective role from the RF positivity is also found with the HLA-DRB1*13 alleles (p = 0.007). As far as the DQB1 locus is concerned, a protective association has been found between the HLA-DQB1*06 alleles with both RF+ and RF+ ACPA+ positivity (p, respectively, 0.05 and 0.04) when comparing the control group with the respective RA patient subgroups. In ACPA+ and RF+ patients compared to the ACPA− and RF− patient subgroups, the only detected difference was between RF (+) and RF (−) patients (p =0.04). CONCLUSION: The relatively low frequencies of DRB1*04 and high (DRB1*11 and DRB1*13) in the Albanian population might explain the rather low positivity rate of ACPA and RF antibodies among the Albanian RA patients. Our study demonstrates that DRB1*11, DRB1*13 and DQB1*06 may be negatively associated with RA. Conversely, DRB1*04 may confer susceptibility to RA in Albanian population.

Molecular typing of HLA-class II alleles reveals an association with autoantibodies and disease subsets of systemic sclerosis in a North Indian (Kashmir) population

To identify specific human leukocyte antigen (HLA)-Class II (DRB/DQB1/DPB1) alleles associated with systemic sclerosis (SSc) and to explore their relation with SSc autoantibodies, clinical manifestations, and disease subsets. HLA-class II alleles (DRB1/DRB3/DRB4/DRB5/DQB1) were determined by DNA typing in 80 SSc cases and 60 matched controls and HLA-DPB1 in 40 SSc patients and 30 controls by allele-specific-polymerase chain reaction with sequence-specific primers (PCR-SSP). The mean age of SSc patients was 36.9 ± 9.4 years; 76 females and 4 males (F:M 19:1) and a disease duration of 5.3 ± 3.3 years, they were 43(53.7%) limited and 37(46.2%) diffuse subtypes. SSc was significantly associated with DRB1*11, DRB1*01, DQB1*04, and DQB1*03*03 in a >4-fold manner, whereas DPB1*04 had a >7-fold increased risk compared to controls. There was a strong association between DRB1*11 (p = 0.04), DQB1*03*03 (p = 0.005), and DPB1*13 (p = 0.009) with anti-topoisomerase I (anti-topoI) whereas the frequency of DRB1*01 (p < 0.0001) was increased in patients with anti-centromere (ACA) positive SSc compared those negative (56% vs 25%; p < 0.0001). DRB1*03, DRB1*15, and DQB1*03*01 were SSc protective alleles in patients with positive ACA. Anti-topo I was associated with interstitial lung disease (ILD) (p < 0.01), whereas ACA with pulmonary arterial hypertension (PAH) (p = 0.01) and protection against ILD (p < 0.001). In addition, HLA-DRB1*03, DQB1*03*01and DPB1*03 were more frequent in patients with ILD than in patients without. Associations between specific HLA-class II alleles with certain SSc-specific autoantibodies (anti-topo I and ACA) were identified. Specific HLA associations with clinical and serological subtypes could serve as biomarkers of disease severity and progression in SSc.

Human leukocyte antigen immunization in transfusion-dependent Moroccan patients with beta-thalassemia major: prevalence and risk factors

IntroductionBeta-thalassemia major patients need a regular blood transfusion to have an initial normal growth. However, these patients have an increased risk of developing alloantibodies. Our main goal was to study HLA alloimmunization in Moroccan Beta-thalassemia patients by confronting it with transfusion and demographic criteria, exploring the involvement of HLA typing profile in the development of HLA antibodies and in turn determining risk factors for their development. MethodsThe study consisted of 53 Moroccan pediatric patients with Beta-thalassemia major. Screening for HLA alloantibodies was performed using Luminex technology Whereas HLA genotyping was done with sequence-specific primers (PCR-SSP). Results: In this study, 50.9% of patients have been identified as positive for HLA antibodies, with 59.3% having both HLA Class I and Class II antibodies. A significant increase frequency of DRB1*11 allele was revealed in non-immunized patients (34.6% vs. 0%, p = 0.001). Our results also revealed that the majority of our HLA immunized patients were women (72.4% vs. 27.6%, p = 0.001), and transfused with more than 300 units of RBC units (66.7% vs. 33.3%, p = 0.02). There were statistically significant differences when comparing these frequencies. ConclusionsThis paper revealed that the transfusion dependent Beta-thalassemia major patients are exposed to risk of developing HLA antibodies following transfusions with leukoreduced RBC units. The HLA DRB1*11 was a protective factor against HLA alloimmunization in our beta-thalassemia major patients.

"Geographical distribution of risk genotypes in pediatric patients with celiac disease in Spain".

Celiac disease is strongly associated with HLA DQ, specifically with haplotypes. DRB1*03-DQA1*05:01/DQB1*02:01 (DQ2.5),DRB1*07-DQA1*02:01/DQB1*02:02 (DQ2.2), DRB1*11-DQA1*05:05/DQB1*03:01 (DQ7.5), and DRB1*04-DQA1*03:01/DQB1*03:02 (DQ8). The distribution of these risk haplotypes in patients with celiac disease is different in the geographical areas investigated. A high frequency of DRB1*07- DQA1*02:01/DQB1*02:02 (DQ2.2) and DRB1*11-DQA1*05:05/DQB1*03:01 (DQ7.5), has been described in Southern Europe. We analyzed 2102 confirmed CD cases with information on both DQB1* alelles and their distribution by geographical area in Spain. According to the presence of this haplotype in one or two chromosomes, the genotype is classified in: DQ2 homozygous, DQ2 heterozygous (cis or trans), DQ8 homozygous, DQ8/DQ2.5, DQ 2.2 homozygous and genotype known as "half DQ2". Two different patterns of risks related to CD were identified. In the Basque Country and Navarre, the Mediterranean Area (Aragon, Catalonia, Valencia, Balearic Islands, and Murcia), the South of Spain (Andalucía and Extremadura), and the Canary Islands, higher frequency of DQ2.5 trans, and more than 80% of DQ2.5/DQ2.2 homozygosis were described. The Cantabrian Coast (Cantabria, Asturias, and Galicia) and Central Areas (Castilla-León and Castilla-La Mancha) showed a higher percentage of DQ2.5/DQ2.5 homozygosis and a lower DQ2.5 in trans frequency, as in Northern Europe. Madrid has an intermediate model between the two described above. 17 cases (0.8%) did not carry any CD risk haplotypes.

Associations of HLA Polymorphisms with Anti-SARS-CoV-2 Spike and Neutralizing Antibody Titers in Japanese Rheumatoid Arthritis Patients Vaccinated with BNT162b2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019. Anti-SARS-CoV-2 spike (S) and neutralizing antibodies (Abs) are measured to evaluate the efficacy of vaccines. Human leukocyte antigen (HLA) may be associated with vaccine efficacy. Here, we investigated the association of HLA polymorphisms with the production of anti-SARS-CoV-2 S or neutralizing Abs in vaccinated rheumatoid arthritis (RA) patients in Japan. Genotyping of DRB1 and DQB1 was conducted in 87 Japanese RA patients vaccinated with BNT162b2. Associations of allele or haplotype carrier frequencies with anti-SARS-CoV-2 S or neutralizing Abs were examined. DRB1*12:01 was significantly positively associated with the production of S Ab (p = 0.0225, odds ratio [OR] 6.08, 95% confidence interval [CI] 1.32-28.03). The DQB1*03:01 allele carrier frequency tended to be higher in high responders of S Ab. Allele carrier frequencies of DRB1*15:01 (p = 0.0102, OR 9.26, 95% CI 1.65-52.01) and DQB1*06:02 (p = 0.0373, OR 7.00, 95% CI 1.18-41.36) were higher in responders of neutralizing Ab. Haplotype and two-locus analyses of DRB1 and DQB1 suggested that DRB1 alleles were the primary drivers of these associations. Logistic regression analysis showed associations of these alleles independent of clinical characteristics. Independent associations were found between HLA alleles and anti-SARS-CoV-2 Ab production by vaccinated RA patients.

Hypoglycemia Caused by Exogenous Insulin Antibody Syndrome: A Large Single-Center Case Series From China.

Exogenous insulin antibody syndrome (EIAS) can lead to unexpected and potentially life-threatening recurrent hypoglycemia. We aimed to better define autoimmune hypoglycemia caused by EIAS in patients with diabetes and shed light on the improvements in the identification and intervention for this rare but possibly life-threatening condition. We summarized the clinical characteristics of autoimmune hypoglycemia caused by EIAS in 23 patients with diabetes. Furthermore, we performed human leukocyte antigen (HLA) genotyping of 10 patients. We identified a high frequency of autoimmune comorbidities (21.7%), food or drug allergy (48%), insulin allergy (30%), lipodystrophy at the insulin injection sites (22%), and antinuclear antibodies (25%) in the patients. Alternation between hyperglycemia and hypoglycemia was observed in more than 90% of the patients. Most patients showed a high insulin autoantibody titer (>90%) and inappropriately increased insulin concentration (insulin/C-peptide molar ratio >7, >85%). We detected similar frequencies of DRB1*0405-DQB1*0401 and DRB1*0901-DQB1*0303 compared with previously reported frequencies in type 1 diabetes, and a lower frequency of DRB1*0406 compared with insulin autoimmune syndrome. The spontaneous remission rate exceeded 70%. Predisposing factors for autoimmune hypoglycemia caused by EIAS include a strong autoimmune background. Susceptible HLA genotypes for type 1 diabetes or insulin autoimmune syndrome might not explain susceptibility to this condition. Additionally, insulin autoantibodies and the insulin/C-peptide molar ratio are reliable screening options. The prognosis for this condition is favorable. Monitoring of insulin and insulin autoantibodies may contribute to treatment effectiveness.

MO206: HLA Frequency in A Spanish Transplant Patients Cohort With ANCA-Associated Vasculitis

Abstract BACKGROUND AND AIMS ANCA-associated vasculitis (AAV) is an autoimmune disease that causes end-stage renal disease in ∼20%–25% of patients who develop kidney failure with progression to end-stage kidney disease with requirement of renal replacement therapy. Previous studies have found a genetic association between some major histocompatibility complex (MHC) loci, like the locus DPB1*0401, and AAV. We conducted a retrospective observational unicentric study with the objective to identify other possible loci related to AAV. METHOD As MHC determination is not usually done in patients with AAV, we looked for patients with AAV included in the kidney transplant list with a complete classic HLA allele determination registered (A, B, C, DR, and DQ). Only 14 patients with diagnosis of AAV included in the kidney transplant list from August 1993 to December 2020 in our hospital centre fulfilled this inclusion criterion. To the statistical analysis, we compared the observed proportion to the theoretical one using a normal test, since the groups in our sample included at least five subjects. We also use a continuity correction factor to approach to a binomial test. RESULTS The highest allele frequency in our cohort were the HLA B*51and the haplotype HLA DRB1*04-DQB1*03:02. We identified a B*51 frequency of 42.8% (6/14 patients) in our AAV register, while its population frequency in Spain is 15%, difference = 27.86% [Confidence interval (CI) 1.93%–53.78%] P = .01. We detected a DRB1*04 frequency of 57.1% (8/14 patients) in our cohort, while the population frequency of DRB1*04 and its associated loci DQB1*03:02 is 22%, difference = 35.14% (CI 9.22%–61.07%) P &amp;lt; .05. CONCLUSION HLA B*51 and the haplotype DRB1*04-DQB1*03:02 are alleles more frequent in patients with AAV than general population. This could translate a genetic predisposition of people with these alleles to develop AAV.

Association between human leukocyte antigen class II (HLA-DRB and -DQB) alleles and outcome of exposure to Mycobacterium tuberculosis: a cross-sectional study in Nairobi, Kenya.

Introductionhuman leukocyte antigen (HLA) class II alleles play an important role in the early immune response to tuberculosis (TB) by presenting antigenic peptides to CD4+ T cells, hence polymorphisms in those genes can influence the efficiency of the immune response to infection and progression to active disease.Methodsan analytical cross-sectional study of adult pulmonary tuberculosis (PTB) patients at Mbagathi County Hospital, Nairobi and their HHCs. Sociodemographic data were captured on questionnaires and clinical data extracted from patient files. Intravenous blood samples were drawn for interferon-gamma release assay (IGRA) to determine latent tuberculosis infection (LTBI) among HHCs, and for extraction of DNA used in typing of HLA-DQB1 and HLA-DRB1 alleles by PCR sequence specific primer amplification. Chi-square and Fisher's exact test were used to compare the HLA type II allele frequencies of LTBI negative HHCs, LTBI positive HHCs and active TB patients. Logistic regression was used to adjust for HIV status.Resultsthe HLA-DQB1 and HLA-DRB1 alleles were analyzed in 17 PTB and 37 HHCs. Nineteen (19) HHCs were LTBI positive, while 18 were LTBI negative. The frequency of DRB3*1 was 0.17-fold lower [95% CI=0.03-0.83] among PTB patients compared to HHCs before adjustment for HIV status (p=0.048). The frequency of the DRB5*2 allele was significantly higher (p=0.013) among PTB patients (23.5%) compared to HHCS (0.00%). After adjusting for HIV status, the frequency of DRB1*14 was 12-fold higher [95% CI=1.11-138.2] among PTB patients compared to HHCs (p=0.040).Conclusionthe higher frequencies of HLA-DRB5*2 and HLA-DRB1*14 alleles in PTB patients suggest a likely association with progression to active PTB. The higher frequency of HLA-DRB3*1 allele among LTBI negative HHCs shows its likely protective role against M. tuberculosis infection in this population.

Immune-mediated thrombotic thrombocytopenic purpura and susceptible HLA alleles

Thrombotic thrombocytopenic purpura (TTP) is an extremely rare and fatal thrombotic disorder characterized by impaired enzyme activity of von Willebrand factor cleaving protease, also known as ADAMTS13. Immune-mediated TTP (iTTP) is an acquired form of TTP caused by the production of auto-antibodies against ADAMTS13. The pathophysiology of autoimmune disorders is multifactorial, with several human leukocyte antigen (HLA) alleles identified as a genetic risk factor for autoimmune diseases known as susceptible HLA. In the early 2010s, three distinct European groups revealed that DRB1*11 is one of the most susceptible alleles in acquiring iTTP among Caucasians based on HLA typing data. Several in silico predictions for allele-restricted ADAMTS13 epitopes against T cells are made in this context, followed by an in vitro validation employing mass spectrometry using eluted peptides and T-cell assays. However, similar analyses in a genetically distinct Japanese population have not yet been conducted. We used next-generation sequencing to perform HLA typing for 52 Japanese patients with iTTP from 19 institutes. Our detailed analysis revealed that the specific allele DRB1*08:03 was identified as a genetic risk factor for iTTP in Japanese patients, but there were no statistically significant differences in the allele frequency of DRB1*11 between iTTP and healthy controls.

Differential HLA Association of GAD65 and IA2 Autoantibodies in North Indian Type 1 Diabetes Patients.

The human leucocyte antigen (HLA) association with type 1 diabetes (T1D) is well known but there are limited studies investigating the association between β-cell autoantibodies and HLA genes. We evaluated the prevalence of GAD65 and IA-2 autoantibodies (GADA and IA2A) in 252 T1D patients from North India and investigated the genetic association of GADA and IA2A with HLA class I and class II genes/haplotypes. GADA and IA2A were detected in 50.79% and 15.87% of T1D patients, respectively, while only 8.73% had both GADA and IA2A. HLA-DRB1∗03 was observed to be significantly higher in GADA+ T1D patients as compared to GADA– (91.41% vs. 66.13%, Bonferroni-corrected P (Pc) = 1.11 × 10−5; OR = 5.45; 95% CI: 2.67-11.08). Similarly, HLA-DQB1∗02 was found to be significantly increased in GADA+ patients (94.53%, Pc = 2.19 × 10−5; OR = 6.27; 95% CI: 2.7-14.49) as compared to GADA– (73.39%). The frequencies of HLA-DRB1∗04 and DQB1∗03 were increased in IA2A+ patients (45.0% and 52.5%, respectively) as compared to that in IA2A– (25.94% and 33.96%, respectively). Further, the frequency of DRB1∗03-DQB1∗02 haplotype was found to be significantly increased in GADA+ T1D patients as compared to GADA- (60.55% vs. 41.94%, P = 3.94 × 10−5; OR = 2.13; 95%CI = 1.49-3.03). Similarly, HLA-DRB1∗04-DQB1∗03 haplotype was found to be significantly increased in IA2A+ T1D patients compared to IA2A– patients (22.5% vs. 12.97%; P = 0.041; OR = 1.95; 95%CI = 1.08-3.52). None of the HLA class I genes (HLA-A, B, and Cw) was found to be associated with GADA or IA2A in people with T1D. Our findings suggest that HLA-DRB1∗03/DQB1∗02 and HLA-DRB1∗04/DQB1∗03 might play an important role in the development of GADA and IA2A, respectively.

HLA polymorphisms and risk of glioblastoma in Koreans.

PurposeImmune responses for cancer cells can be altered according to genetic variation of human leukocyte antigen (HLA). Association of HLA polymorphism with risk of various cancer types is well known. However, the association between HLA and glioblastoma (GBM) remains uncertain. We sought to evaluate the association of HLA polymorphism with risk of GBM development in Koreans.Materials and methodsA case-control study was performed to identify the odds ratios (OR) of HLA class I and II genes for GBM. The control group consisted of 142 healthy Korean volunteers, and the GBM group was 80 patients with newly diagnosed GBM at our institution. HLA class I (-A, -B, and–C) and class II (-DR, -DQ, and–DP) genotyping was performed by high-resolution polymerase chain reaction (PCR)-sequence-based typing (PCR-SBT) methods.ResultsThere were significantly decreased frequencies of HLA-A*26:02 (OR 0.22 CI 0.05–0.98), HLA-C*08:01 (OR 0.29 CI 0.10–0.87), and HLA-DRB1*08:03 (OR 0.32 CI 0.11–0.98), while there was significantly increased frequency of HLA-C*04:01 (OR 2.29 CI 1.05–4.97). In analysis of haplotypes, the frequency of DRB1*14:05-DQB1*05:03 was significantly decreased (OR 0.22 CI 0.05–0.98).ConclusionThis study suggests that genetic variations of HLA may affect GBM development in Koreans. Further investigations with larger sample sizes are needed to delineate any potential role of the HLA polymorphisms in the pathogenesis of GBM development.

HLA-DRB1 alleles as predisposing and resisting factor in women suffering from vulvovaginal candidiasis

BackgroundVulvovaginal candidiasis (VVC) is a vaginal mucosal infection that usually affects women in their reproductive age. When the signs of VVC persist on a daily basis or last for a long time and repeat at least three times per year, the disease is considered chronic and recurrent. ObjectiveThe purpose of this study was to evaluate the frequency of HLA-DRB1 alleles in patients with recurrent vulvovaginal candidiasis (RVVC). Study design120 patients with RVVC and 136 age-matched healthy controls underwent low-resolution HLA-DRB typing performed using the polymerase chain reaction-sequence-specific primers (PCR-SSP) technique. ResultsIn the present work, we studied different genes that encode HLA-DRB (HLA-DRB1 / HLA-DRB3 / HLA-DRB4 / HLA-DRB5) and showed that HLA-DRB1×14, found in 25% of the patients. In the present study, the significant frequency of HLA-DRB1×10 in the control group suggests a resistant role of this allele to RVVC infections ConclusionsIn the HLA-DRB region, the DRB1×14 allele showed a higher frequency in the patients with RVVC than in the controls. Moreover, the higher frequency of DRB1×10 observed in the controls than in the patients with RVVC. These results demonstrate the HLA-DRB1 alleles are in relation with both susceptibility and immunity factors in RVVC infection and possible susceptible role of HLA-DRB1×14