Viral selection pressure and CD4+T cell epitope in HLA-DRB1 * 11:01 of HCV infected patients / 中国输血杂志

【Objective】 HLA-DRB1 * 11:01, as a class HLA-Ⅱ gene, was reported to be associated with spontaneous clearance of HCV in Han and Li population. Our study was to investigate the effects of viral selection pressure and CD4+T cell epitope on the natural outcome of HCV infection in HLA-DRB1 * 11:01 positive infected patients. 【Methods】 The positive selection sites and population growth of E1E2 and NS3 genes of common HCV 6a in HLA-DRB1 * 11:01 positive and negative groups in Guangdong were respectively analyzed. The peptide library covering the conserved regions of common HCV genotypes was used to stimulate HCV spontaneous clearance group and chronic infection group using ELISPOT method. Reactive peptides were obtained according to the number of spot-forming cells per well and the frequency of occurrence in different groups. 【Results】 The positive selection sites (PSSs) of E1E2 and NS3 of common HCV 6a in HLA-DRB1 * 11:01 negative group were greater than those in HLA-DRB1 * 11:01 positive group. Furthermore, the number of PPSs in CD4+T cell peptide in HLA-DRB1 * 11:01 negative group were also greater than those in HLA-DRB1 * 11:01 positive group; Both groups of HCV 6a had a population growth in Guangdong, and the expansion trend of HLA-DRB1 * 11:01 negative group was significantly higher than that of HLA-DRB1 * 11 :01 positive group. Compared to HCV chronic infection group, the response rate of HCV spontaneous clearance group to five peptides (C-52 E2691-707, C-119 NS31545-1560, C-134 NS4A1669-1684, C-154 NS4B1912-1927, C-159 NS4B1929-1944) was higher. However, the HCV chronic infection group showed a higher response rate to two of the peptides(C-111 NS31497-1512, C-130 NS31650-1665). When HLA-DRB1 * 11:01 typing was considered, there was no significant difference in HCV-specific immune response generated by PBMCs between HLA-DRB1 * 11:01 positive and HLA-DRB1 * 11:01 negative groups. 【Conclusion】 This study revealed the relationship between viral selection pressure of HLA-DRB1 * 11:01 HCV infected persons and CD4+T cell antigen epitopes. At the same time, CD4+ T cell antigen epitopes of HCV pan-genotype were obtained, providing basic data for the development of T cell vaccine suitable for HCV pan-genotype.

HLA-DQA1*04: 01 is related to a higher multiple sclerosis lesion load on T2/Flair MRI sequences / O HLA-DQA1*04: 01 está relacionado com uma alta carga lesional na ressonância magnética em T2/Flair nos pacientes com esclerose múltipla

ABSTRACT Background: The genetic predisposition to multiple sclerosis (MS) is associated with HLA alleles, especially HLA-DRB1*15:01. Objective: To identify associations between findings in magnetic resonance imaging (MRI) and genetic features in a Brazilian cohort of patients with MS. Methods: We retrospectively studied data from 95 consecutive patients with MS. Two independent observers who were blinded to the clinical data identified black holes and enhanced lesions on T1 MRI sequences, and counted and measured contrast-enhanced lesions on T2 and Flair (fluid attenuation inversion recovery) sequences. Cases were classified according to lesion size, number, and volume. The HLA-DRB1, HLA-DQB1, and HLA-DQA1 alleles, and the rs4774, rs3087456, rs6897932, rs731236, and rs1033182 single nucleotide polymorphisms were identified by polymerase chain reaction amplification with sequence-specific primers using the One Lambda Inc. Kit, Canoga Park, CA, USA. Results: Patients with the HLA-DQA1*04:01 allele had lesion load (adjusted for age, sex, and MS duration) above median compared with patients with other HLA-DQA1 alleles (p=0.02). There were no differences among all the other HLA alleles and single nucleotide polymorphisms and lesion load. Conclusions: The correlation of the HLA-DQA1*04:01 allele with a higher lesion load on T2/Flair MRI sequences suggests that the presence of this allele is associated with the risk of greater MS severity.

RESUMO Antecedentes: A predisposição genética para a esclerose múltipla (EM) está associada a alelos HLA, principalmente o HLA-DRB1*15:01. Objetivo: Identificar associações entre lesões na ressonância magnética e características genéticas em uma coorte brasileira de pacientes com EM. Métodos: Estudamos retrospectivamente os dados de 95 pacientes consecutivos com EM. Dois observadores independentes que desconheciam os dados clínicos identificaram "black holes" e lesões realçadas pelo contraste nas sequências de ressonância magnética T1 e contaram e mediram as lesões nas sequências T2 e FLAIR (fluid attenuated inversion recovery). Os casos foram classificados de acordo com tamanho, número e volume da lesão. Os alelos HLA-DRB1, HLA-DQB1 e HLA-DQA1 e os polimorfismos de nucleotídeo único rs4774, rs3087456, rs6897932, rs731236 e rs1033182 foram identificados por amplificação de reação em cadeia da polimerase com iniciadores específicos de sequência usando o kit One Lambda Inc., Canoga Park, CA, EUA. Resultados: Os pacientes com alelo HLA-DQA1*04:01 apresentaram carga de lesão (ajustada para idade, sexo e duração da EM) acima da mediana em comparação com outros pacientes com demais alelos HLA-DQA1 (p=0,02). Não houve diferenças entre todos os outros alelos HLA e polimorfismos de nucleotídeo único e carga lesional. Conclusões: A correlação do alelo HLA-DQA1*04:01 com maior carga de lesão nas sequências de RM em T2 sugere que a presença desse alelo pode estar associada ao risco de maior gravidade da EM.

Correlation between HLA-DQB1 and HLA-DRB1 gene polymorphisms and caries: a systematic review and Meta-analysis / 口腔疾病防治

Objective@#Systematic evaluation of the correlation of HLA-DQB1 and HLA-DRB1 allele polymorphisms with caries, to provide reference for caries prevention and treatment. @*Methods@# Relevant literature published before December 2020 was searched in the Cochrane Library, PubMed, Embase, Web of Science, Scopus, CNKI, Wanfang, VIP, and CBM databases. Meta-analysis was performed using the R4.0.2 software to test for heterogeneity and evaluate the publication bias.@*Results @# In total,10 case-control studies were included with 564 people in the case group and 676 people in the control group. The results of the Meta-analysis show that: ① HLA-DQB1*02 (OR=0.52, 95%CI=0.29-0.93, P < 0.05) and HLA-DRB1*09 (OR=0.34, 95%CI=0.21-0.58, P < 0.05) are protective factors of dental caries; ② HLA-DRB1*13 (OR=2.96, 95%CI=2.03-4.33, P < 0.05) and HLA-DRB1*14 (OR=1.95, 95%CI=1.26-3.02, P < 0.05) alleles are risk factors for the development of dental caries. The results of the subgroup analysis are: HLA-DRB1*07 is a caries susceptibility factor in the Chinese population (OR=0.48, 95% CI=0.24-0.97, P < 0.05), while it is not statistically significant in the Brazilian and Turkish populations; HLA-DRB1*11 is a caries protective factor in the saliva group (OR=2.26, 95% CI=1.46-3.52, P < 0.05). 3.52, P < 0.001), while it is a caries susceptibility factor in the blood group (OR=0.09, 95% CI=0.12-0.34, P < 0.001). @*Conclusion @#HLA-DRB1*13 and HLA-DRB1*14 alleles are caries susceptibility genes, and HLA-DQB1*02 and HLA-DRB1*09 have protective effects on the caries development. HLA-DRB1*07 is a caries susceptibility gene in the Chinese population; HLA-DRB1*11 is a caries protective gene in the saliva group. Due to the limited sample size and quality of the included studies, more high-quality studies will be included later for verification.

Examining Caries Risk With the Caracteristic of HLA-DRB1 Gene

@#Introduction: HLA-DRB1 alleles were derived from MHC class II molecules. These alleles encoded sIgA secretion which contribute as a barrier to S. mutans colonization. HLA-DRB1 was known as genes with high mutations causing differences in peptide bond, thus affecting the progression and vulnerability to a disease. The purpose of this study was to determine the effect of mutations in HLA-DRB1 alleles in different dental caries risk. Methods: In this study, we extracted the genomic DNA from whole blood samples of 30 patients with low level dental caries (indeks def-t < 2) as control group and high level dental caries (deft > 3) as case group. HLA-DRB1 varians were studied through genomic DNA isolation for PCR-RFLP. RFLP is analyzed through BseRI, BsaJI, RsaI, and Sau961 restriction enzymes was used in this assay. Results: The PCR-RFLP typing method was evaluated on 60 genomic DNA samples, result found that all samples were divided into 5 groups of variants, two variants in the control group and three variants in the case group. Conclusion: PCR-RFLP was shown to be a sensitive method for the detection of mutation in HLADRB1 alleles caused a dental caries level differences. HLA-DRB mutations caused changes in signal transduction and therefore contributes to imunogenetik pathway of dental caries.

Polimorfismos do gene HLA-DRB1 em pacientes pediátricos com hepatite autoimune tipo 1 e hepatite autoimune associada à colangite autoimune / Hla-drb1 gene polymorphisms in pediatric patients with type 1 autoimmune hepatitis and type 1 autoimmune hepatitis overlap syndrome with autoimmune cholangitis

ABSTRACT BACKGROUND: Autoimmune hepatitis (AIH) is a rare chronic inflammatory liver disease associated with a loss of immunological tolerance to self-antigens. Susceptibility to AIH is partially determined by the presence of genes related to human leukocyte antigen (HLA), mainly allelic variants of DRB1. OBJECTIVE: The purpose of this study was to investigate the frequencies of the polymorphisms in HLA-DRB1 gene in children and adolescents with type 1 AIH and type 1 AIH overlap syndrome with autoimmune cholangitis (overlap syndrome, OS) in comparison to healthy sex and age-matched individuals (control group). METHODS: This is a cross-sectional study of 25 pediatric patients diagnosed with type 1 AIH and 18 with OS. Fifty-seven healthy individuals were included as controls. The polymorphisms of the HLA-DRB1 gene were evaluated by PCR and included HLA-DRB1*03, HLA-DRB1*04, HLA-DRB1*07, and HLA-DRB1*13. RESULTS: Our results showed that the presence of the allele HLA-DRB1*13 increased the chance of autoimmune cholangitis (OR=3.96, CI 1.07 to 14.61, P=0.04). The HLA-DRB1*04 and HLA- DRB1*07 have no association with the AIH and autoimmune cholangitis in a young sample. CONCLUSION: This work demonstrates an association of the main polymorphisms in the HLA-DRB1 gene to AIH with or without cholangitis in a Brazilian sample.

RESUMO CONTEXTO: Hepatite autoimune (HAI) é uma doença hepática inflamatória crônica, rara, associada à perda da tolerância imunológica aos auto-antígenos. A susceptibilidade à HAI é parcialmente determinada pela presença de genes relacionados ao antígeno leucocitário humano (HLA), principalmente variantes alélicas do DRB1. OBJETIVO: O objetivo deste estudo foi investigar a frequência de polimorfismos no gene HLA-DRB1 em crianças e adolescentes com HAI tipo 1 e HAI tipo 1 associada à colangite autoimune, em comparação com indivíduos saudáveis pareados por sexo e idade (grupo controle). MÉTODOS: Este é um estudo transversal de 25 pacientes pediátricos com diagnóstico de HAI tipo 1 e 18 com HAI associada à colangite autoimune. Cinquenta e sete indivíduos saudáveis foram incluídos como controles. Os polimorfismos do gene HLA-DRB1 foram avaliados por PCR e incluíram HLA-DRB1*03, HLA-DRB1*04, HLA-DRB1*07 e HLA-DRB1*13. RESULTADOS: Nossos resultados mostraram que a presença do alelo HLA-DRB1*13 aumentou a chance de colangite autoimune (OR=3,96; IC 1,07 a 14,61; P=0,04). O HLA-DRB1*04 e o HLA-DRB1*07 não apresentam associação com a HAI e colangite autoimune no grupo de pacientes mais jovens. CONCLUSÃO: Este trabalho demonstra uma associação dos principais polimorfismos no gene HLA-DRB1 à HAI com ou sem colangite na população brasileira.

Association between human leukocyte antigen-DRB1 and human leukocyte antigen-DQB1 alleles and pemphigus vulgaris in Indian patients: A case–control study

Background: HLA-DRB1*04, -DRB1*08, -DRB1*14, -DQB1*03 and -DQB1*05 are reported to have significant association with pemphigus vulgaris; however, this is partially dependent on ethnicity. This study was done to determine the HLA-DR and -DQ types prevalent in Indian patients with pemphigus vulgaris. Methods: A prospective case–control study was done for a period of 9 months in Christian Medical College Vellore, India. HLA typing was done by PCR-SSOP method in 50 cases and 50 healthy controls. Allele frequencies in cases and controls were compared and odds ratios with 95% confidence interval were calculated. Results: The mean age of the patients (29 females, 21 males) and that of controls (36 males, 14 females) were 41.3 ± 13.65 and 35.42 ± 11.09 years, respectively. HLA-DRB1*14 was present in 47 patients and 18 controls (OR, 27.85; 95% CI, 7.57–102.42) and HLA-DQB1*05 was seen in 47 patients and 24 controls (OR, 16.97; 95% CI, 4.66–61.80). The haplotype DRB1*14, DQB1*05 was present in 44 patients and 14 controls (OR, 18.86; 95% CI, 6.58–54.05). DRB1*15 was present in 7 cases and 16 controls (OR, 0.35; 95% CI, 0.13–0.94) and DQB1*06 was present in 8 cases and 19 controls (OR, 0.31; 95% CI, 0.12–0.80). HLA-DQB1*03 was associated with significantly higher pemphigus disease area index scores. Limitations: The main limitations were that the numbers studied were small as the study was conducted at a single center, and the haplotype analysis was limited only to the proband. PDAI scores could have been influenced by prior treatment. Conclusion: There was a significant association between HLA-DRB1*14 and HLA-DQB1*05 and pemphigus vulgaris in our patients. A negative association was seen with DRB1*15 and DQB1*06.

Prevalence, Risk Factors, and Expression of Human Leukocyte Antigen-DRB1 in Juvenile Idiopathic Arthritis-associated Uveitis

OBJECTIVE: This study investigated the prevalence and risk factors of juvenile idiopathic arthritis (JIA)-associated uveitis (JIA-U) in a pediatric tertiary center in Korea. In addition, this study examined whether a specific HLA-DRB1 allele could be a predictive risk factor of uveitis in JIA. METHODS: The pediatric rheumatology and ophthalmology medical records for JIA between March 2006 and March 2016 were analyzed retrospectively. A total of 233 were enrolled in this study. RESULTS: Of 233 patients, 31 developed uveitis (13.3%): 14 oligoarticular, three polyarticular, six systemic, seven enthesitis-related, and one undifferentiated-type JIA. In oligoarticular JIA, 26.4% developed uveitis. The percentage of females with JIA-U was 54.8%, and the median age of the onset of JIA was 7.02 years in JIA-U. Antinuclear antibody (ANA) positivity in oligoarticular JIA-U was 57.1%. Of the 31 JIA-U cases, 26 (83.9%) were clinically asymptomatic when diagnosed. The allele frequency of HLA-DRB1*09 of the total JIA-U was higher than that of JIA without uveitis. HLA-DRB1*09 and HLA-DRB1*12 were higher in oligoarticular JIA-U than in JIA without uveitis. CONCLUSION: Korean JIA-U has different features from JIA-U in Western countries. The sex ratio and age of JIA onset showed no significant differences in Korean JIA-U. The ANA positivity was more common in JIA-U than in JIA without uveitis only in oligoarticular type JIA. These differences might be due to genetic factors, particularly HLA-DRB1. These results suggest HLA-DRB1*09 and HLA-DRB1*12 in oligoarticular JIA to be risk factors for JIA-U in Korea. This is the first study to analyze the association between HLA-DRB1 and JIA-U in Korea.

Association of and Polymorphisms with Risk of Systemic Lupus Erythematosus / 中华医学杂志(英文版)

Background@#Systemic lupus erythematosus (SLE) is an autoimmune disease under genetic control. Growing evidences support the genetic predisposition of HLA-DRB1 gene polymorphisms to SLE, yet the results are not often reproducible. The purpose of this study was to assess the association of two polymorphisms of HLA-DRB1 gene (HLA-DR3 and HLA-DR15) with the risk of SLE via a comprehensive meta-analysis.@*Methods@#This study complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Case-control studies on HLA-DRB1 and SLE were searched from PubMed, Elsevier Science, Springer Link, Medline, and Cochrane Library database as of June 2018. Analysis was based on the random-effects model using STATA software version 14.0.@*Results@#A total of 23 studies were retained for analysis, including 5261 cases and 9838 controls. Overall analysis revealed that HLA-DR3 and HLA-DR15 polymorphisms were associated with the significant risk of SLE (odds ratio [OR]: 1.60, 95% confidence interval (CI): 1.316-1.934, P = 0.129 and OR: 1.68, 95% CI: 1.334-2.112, P = 0.001, respectively). Subgroup analyses demonstrated that for both HLA-DR3 and HLA-DR15 polymorphisms, ethnicity was a possible source of heterogeneity. Specifically, HLA-DR3 polymorphism was not associated with SLE in White populations (OR: 1.60, 95% CI: 1.320-1.960, P = 0.522) and HLA-DR15 polymorphism in East Asian populations (OR: 1.65, 95% CI: 1.248-2.173, P = 0.001). In addition, source of control was another possible source for both HLA-DR3 and HLA-DR15 polymorphisms, with observable significance for HLA-DR3 in only population-based studies (OR: 1.65, 95% CI: 1.370-1.990, P = 0.244) and for HLA-DR15 in both population-based and hospital-based studies (OR: 1.38, 95% CI: 1.078-1.760, P = 0.123 and OR: 2.08, 95% CI: 1.738-2.490, P = 0.881, respectively).@*Conclusions@#HLA-DRB1 gene may be a SLE-susceptibility gene, and it shows evident ethnic heterogeneity. Further prospective validations across multiple ethnical groups are warranted.

Asociación genética entre los Loci HLA-DRB1 y HLA-DQB1 con la susceptibilidad a padecer Lupus eritematoso sistemático / Genetic association between the Loci HLA-DRB1 and HLA-DQB1 with susceptibility to suffer from systemic lupus erythematosus

La investigación en Inmunogenética brinda información acerca de marcadores genéticos asociados con enfermedades autoinmunes, como el Lupus Eritematoso Sistémico (LES), se puede observar entonces ciertos factores de riesgo o protección hacia la enfermedad en una población determinada. OBJETIVO: Determinar la asociación genética entre los polimorfismos del Complejo Principal de Histocompatibilidad (CPH) representados por los loci HLA-DRB1 y HLA-DQB1 con la susceptibilidad a LES. METODOLOGÍA: Se trabajó con 85 pacientes lúpicos y 85 pacientes sin la enfermedad; se obtuvo DNA humano a partir de sangre periférica, se realizó un PCR-SSP de baja y alta resolución para tipificar molecularmente a los loci HLA-DRB1 y HLA-DQB1. Se determinó las frecuencias alélicas, las cuales fueron asociadas con ambas muestras mediante el uso del Odds Ratio, a un nivel de significancia del 5 %. RESULTADOS: Los resultados del PCR-SSP de baja resolución muestran que ningún alelo HLA tiene un rol predisponente, se observó que el alelo HLA-DRB1*04 presenta un rol protector OR=0,49 (p=0,03). Los resultados por PCR-SSP de alta resolución muestran que los alelos HLA-DRB1*03:01 (OR=18,3; p=0,007), DRB1*04:04 (OR=4,2; p=0,009), DRB1*09:01 (OR=18,3; p=0,007), HLA-QB1*03:03 (OR=18,8; p=0,006) y DQB1*02:01 (OR=21,2; p=0,003) son factores de riesgo. Se evidenció que los alelos HLA-DRB1*08:02 (OR=0,42; p=0,003) y HLA-DQB1*04:02 (OR=0,50; p=0,02) son de carácter protector. CONCLUSIONES: Los alelos que representan riesgo de padecer LES en la muestra estudiada son HLA-DRB1*03:01, 04:04, 09:01 y HLA-DQB1*03:03, 02:01. Los alelos que tiene un carácter protector a la enfermedad son HLA-DRB1*08:02 y HLA-DQB1*04:02.

Immunogenetics research provides information on genetic markers associated with autoimmune diseases such as systemic lupus erythematosus (SLE), you can then observe certain risk factors or protection to the disease in a given population. To determine the genetic association between polymorphisms of the Major istocompatibility Complex loci represented by the HLA-DRB1 and HLA-DQB1 with susceptibility to SLE. METHODOLOGY: We worked with 85 lupus patients and 85 patients without the disease; Human DNA was obtained from peripheral blood, PCR-SSP low and high resolution molecularly performed to establish the loci HLA-DRB1 and HLA-DQB1. Allele frequencies, which were associated with both samples using the Odds Ratio at a level of significance of 5% were determined. RESULTS: Results of PCR-SSP low-resolution HLA show that no predisposing allele plays a role, we observed that HLA-DRB1*04 allele has a protective role OR=0.49 (p=0.03). The PCR-SSP results of high resolution show that the HLA-DRB1*03:01 alleles (OR=18.3; p=0.007), DRB1*04:04 (OR=4.2; p=0.009), DRB1*09:01 (OR=18.3; p=0.007), HLA-QB1*03:03 (OR=18.8; p=0.006) and DQB1*02:01 (OR=21.2; p=0.003) are risk factors. We demonstrated that HLA-DRB1*08:02 alleles (OR=0.42; p=0.003) and HLA-QB1*04:02 (OR=0.50; p=0.02) are of a protective nature. CONCLUSIONS: The alleles representing LES risk in the study sample are HLA-DRB1*03:01, *04:04, *09:01 and HLA-DQB1*03:03, *02:01. The alleles having a protective character to the disease are HLADRB1* 08:02 and HLA-DQB1*04:02.

Correlation between HLA-DB1 genes and susceptibility to echinococcosis in Tibetan population in Tibetan Plateau / 中国血吸虫病防治杂志

Objective To determine the susceptibility genes and resistance genes in HLA-DRB1 alleles in Tibetan patients with cystic and alveolar hydatid diseases,so as to provide the references for the research of the genetic characteristics and infec-tion mechanism of Tibetan hydatid diseases. Methods The case control method was applied. The Tibetan patients with cystic and alveolar hydatid diseases(63 and 73 cases respectively)in Yushu and Guoluo Tibetan Autonomous Prefecture,and unrelat-ed healthy people(60 cases)in this area were selected as the study subjects. The polymerase chain reaction-sequence based typ-ing(PCR-SBT)technique was applied for genotyping of HLA-DRB1,and the comparison of the gene frequency. Results The frequency of HLA-DRB1*04 in the alveolar/cystic echinococcosis group was lower than that in the control group(χ2 =4.71, 4.31,both P<0.05). Conclusion HLA-DRB1*04 genotypes may be associated with the resistance of cystic and alveolar echi-nococcosis and its resistance genes.

Association analysis between HLA-DRB1 alleles and pemphigus vulgaris in a Han population in Sichuan / 中华皮肤科杂志

Objective To investigate the association between HLA-DRB1 alleles and pemphigus vulgaris (PV) in a Han population in Sichuan.Methods Polymerase chain reaction with sequencespecific primer (PCR-SSP) method was used for low-resolution and high-resolution typing of HLA-DRB1 alleles in 19 patients of Han nationality with PV and 25 healthy controls in Sichuan.Allele frequencies were calculated,and differences in the allele frequency between the above two groups were compared by using chisquare test.Results Totally,9 kinds of DRB 1 low-resolution alleles and 19 kinds of DRB 1 high-resolution alleles were identified in the PV patients and healthy controls.Frequencies of the DRB1* 14 allele (39.47％[15/38] vs.8.00％[4/50],x2 =17.43,P ＜ 0.05) and DRB1*1405 allele (15.79％[6/38] vs.2.00％[1/50],x2 =4.25,P ＜ 0.05) were significantly higher in the PV patients than in the healthy controls.Conclusion The HLA-DRB1*14 allele may be a common susceptibility gene for PV in the Han population in Sichuan,and the HLA-DRB1* 1405 allele may be most closely associated with PV.

Relevance analysis on HLA-DRB1 alleles andocculthepatits B virus infection / 中国输血杂志

Objective To study the HLA-DRB1 genotupe and their relation with OBI infection.Methods HLA-DRB1 genotyping was conducted in 102 patients OBI infection and 201 health controls,by using polymerase chain reaction sequence-based typing (PCR-SBT)method.The association between HLA-DRB1 genotype and OBI was also studied.Results Compared to 201 health controls,the allele frequency of HLA-DRB1 * 0405 (1.980 4％) (x2 =12.477 0,P =0.000 0,OR =16.367 3) * 0803 (4.257 3％) (x2 =30.689 8,P =0.000 0,OR =36.454 5)、* 1101 (5.545 9％) (x2 =4.471 2,P =0.034 5,OR =1.903 8)、* 1201 (1.481 6％) (x2 =8.591 9,P =0.003 4,OR =12.151 5) were markedly higher.The allele frequency of HLA-DRB1 * 0701(2.230 8％) (x2 =5.585 5,P=0.018 1,OR=0.417 7)、* 1301 (0.245 4％) (x2 =4.513 7,P=0.033 6,OR=0.147 4) 、* 1302(0.491 4％) (x2=11.369 1,P=0.000 7,OR=0.000 0) 、* 1312(0.245 4％) (x2 =5.0198,P=0.025 1,OR=0.136 5) 、* 1501(4.257 3％) (x2=10.763 1,P=0.001 0,OR=0.000 0)was obviously lower than than in HBV patients.Conclusion HLA-DRB1 * 0701、* 1301、* 1302、* 1312、* 1501 are closely related with susceptibility to OBI,and HLA-DRB1 * 0405、* 0803、* 1101、* 1201 is closely related with resistance to OBI.

The role of KIR2DL3/HLA-C*0802 in Brazilian patients with rheumatoid vasculitis

OBJECTIVES: Rheumatoid arthritis is a polygenically controlled systemic autoimmune disease. Rheumatoid vasculitis is an important extra-articular phenotype of rheumatoid arthritis that can result in deep cutaneous ulcers. The objective of this study was to establish a correlation between the frequency of major histocompatibility complex class I/II alleles and killer immunoglobulin-like receptor genotypes in patients with cutaneous rheumatoid vasculitis. METHODS: Using the Scott & Bacon 1984 criteria to diagnose rheumatoid vasculitis and after excluding any other causes such as diabetes, atherosclerosis, adverse drug reactions, infection, and smoking, patients who met the criteria were selected. All of the selected rheumatoid vasculitis patients presented deep cutaneous ulcers. Identification of the major histocompatibility complex class I/II and killer immunoglobulin-like receptor genotypes was performed by polymerase chain reaction assays of samples collected from the 23 rheumatoid vasculitis patients as well as from 80 controls (40 non-rheumatoid vasculitis RA control patients and 40 healthy volunteers). RESULTS: An association between the presence of the HLA-DRB1*1402 and HLA-DRB1*0101 alleles and cutaneous lesions in rheumatoid vasculitis patients and a correlation between the inhibitor KIR2DL3 and the HLA-C*0802 ligand in rheumatoid vasculitis patients were found. CONCLUSION: An association was found between the presence of the HLA-DRB1*1402 and HLA-DRB1*0101 alleles and the development of cutaneous lesions in rheumatoid vasculitis patients. Additionally, the HLA-C*0802 ligand protects these individuals from developing cutaneous lesions. .

The CIITA genetic polymorphism rs4774*C in combination with the HLA-DRB1*15:01 allele as a putative susceptibility factor to multiple sclerosis in Brazilian females / O polimorfismo rs4774*C no gene CIITA em conjunção com o alelo HLA-DRB1*15:01 é um possível fator de susceptibilidade a esclerose múltipla em mulheres brasileiras

The objective of this study was to investigate the association between the HLA alleles at the DQA1, DQB1 and DRB1 loci, the CIITA genetic polymorphisms -168A/G and +1614G/C, and susceptibility to multiple sclerosis (MS) in a sample from Rio de Janeiro State, Brazil. Furthermore, we wished to determine whether any of these associations might be more significant in women compared with men. DNA samples from 52 relapsing-remitting MS (RRMS) patients and 126 healthy controls matched for sex and age were analyzed. We identified a significant HLA-DRB1*15:01-MS association that was female-specific (Odds Ratio (OR) = 4.78; p = 0.001). Furthermore, we observed that the +1614G/C mutation in combination with the HLA-DRB1*15:01 allele increased susceptibility to MS in females (OR = 4.55; p = 0.01). Together, these findings highlight the polygenic nature of MS.

O objetivo deste estudo foi investigar a associação entre alelos HLA, loci DQA1, DQB1 e DRB1, polimorfismos -168A/G e +1614G/C no gene CIITA, e suscetibilidade à esclerose múltipla (EM) em uma amostra de Rio de Janeiro, Brasil. Além disso, buscou-se determinar se alguma dessas associações pode ser gênero-dependente. Foram analisadas amostras de DNA de 52 pacientes com EM reincidente-remitente (EMRR) e 126 controles saudáveis ​​pareados por sexo e idade. Foi identificada associação significativa HLA-DRB1*15:01-EMRR, que foi específica para o gênero feminino (Odds Ratio (OR) = 4,78, p = 0,001). Além disso, observou-se que o polimorfismo +1614 G/C, em combinação com o alelo HLA-DRB1*15:01 provoca o aumento da susceptibilidade à EM em pacientes do sexo feminino (OR = 4,55, p = 0,01). Juntos, estes resultados destacam a natureza poligênica da EM.

Antígenos HLA de clase ii en pacientes con artritis reumatoide ecuatorianos y asociación con el factor reumatoide, anticuerpos anti-citrulinados y nódulos reumatoides / HLA antigens class ii in patients with ecuadorian rheumatoid arthritis and association with the rheumatoid factor, anti-citrulinated antibodies and rheumatoid nodules

Objetivo Determinar los antígenos de Clase II en 52 pacientes con artritis reumatoide (AR) y 52 controles, y establecer la asociación de los antígenos de Clase II DRB1* con el factor reumatoide (FR), anticuerpos anti-péptido cíclico citrulinados (anti-CCP) y nódulos reumatoides. Material y Métodos Estudio de casos y controles, realizado en pacientes del Hospital Vicente Corral Moscoso y José Carrasco Arteaga de la ciudad de Cuenca-Ecuador; se incluyeron 52 pacientes con AR que cumplen los criterios del Colegio Americano de Reumatología (ACR) y 52 controles. Se identificaron a través de la Reacción en Cadena de la Polimerasa (PCR), los diferentes tipos de HLA que tienen cada uno de los 52 pacientes con AR y controles. Se buscó asociación de los HLA-DR1* con la AR y las pruebas de laboratorio: FR, anticuerpos anti-CCP y con nódulos reumatoides. El análisis estadístico se realizó con el cálculo de OR (IC 95%) y 2 de Pearson con corrección de Fisher y la información se procesó en SPSS v15. Resultados Los alelos más frecuentes fueron HLA-DRB1*09 (17,3%) OR 3,42 (IC95% 1,21 ­ 10,14) y HLADRB1*04 (32,7%) OR 1,81 (IC95% 0,93 ­ 3,55). Tanto el factor reumatoide como los anticuerpos anti-péptido cíclico citrulinados estuvieron presentes en el 82,7% de pacientes con artritis reumatoide y los nódulos reumatoides se detectaron en el 19,2% de pacientes con AR. Se encontró asociación entre los nódulos reumatoides con valores altos de FR y anti-CCP y estos a su vez con los alelos HLA-DRB1*14 y HLADRB1*04. La mayoría de pacientes con alelos HLA-DRB1*09 con predominio heterocigoto tuvieron anticuerpos anti-CCP y FR positivo. Conclusión La presencia de los alelos HLA-DRB1*04 y HLADRB1*09 está relacionada con la susceptibilidad de presentar AR en pacientes ecuatorianos, además se relaciona con valores elevados de factor reumatoide y anticuerpos anti-péptido cíclico citrulinados.

Objective To determine Class II antigens in 52 patients with rheumatoid arthritis (RA) and 52 controls and establish the association of Class II antigens DRB1* with rheumatoid anti- cyclic citrullinated peptide (anti-CCP) rheumatoid factor (RF), and antibodies rheumatoid nodules. Methods and Materials Case and control study in patients from the Hospital Vicente Corral Moscoso and José Carrasco Arteaga of Cuenca-Ecuador; 52 patients with rheumatoid arthritis who satisfy the criteria of ACR-American College of Rheumatology and 52 healthy patients. The different types of HLA from each 52 patients with rheumatoid arthritis and controls were identified through PCR - Polymerase Chain Reaction. Association of HLA-DR1* with rheumatoid arthritis and rheumatoid factor, anti-citrullinated and rheumatoid nodules. The statistical analysis was done by the OR (IC 95%) and 2 of Pearson with Fisher correction and the information was processed in SPSS v15. Results The most frequency alleles were HLA-DRB1*09 (17,3%) OR 3,42 (IC95% 1,21 ­ 10,14) and HLADRB1*04 (32,7%) OR 1,81 (IC95% 0,93 ­ 3,55). The rheumatoid factor and anti-cyclic citrullinated peptide antibodies were presented in 82,7% of patients with rheumatoid arthritis and rheumatoid nodules was detected in the 19.2% of patients with rheumatoid arthritis . An association between rheumatoid nodules with high values of rheumatoid factor and anti-ccp and these in turn with HLA-DRB1*14 y HLA-DRB1*04 alleles were found. The majority of patients with HLA-DRB1*09 alleles with heterozygote predomination had positive anti-ccp and rheumatoid factor. Conclusion The presence of HLA-DRB1*04 and HLA-DRB1*09 alleles is related with the susceptibility of present rheumatoid arthritis in Ecuadorian patients, and it is related with higher values of rheumatoid factor and anti-cyclic citrullinated peptide.

Interaction between HLA-DRB1 gene polymorphism and environmental risk factors in the development of gestational diabetes mellitus / 中华妇产科杂志

Objective To explore the interactions between human leukocyte antigen ( HLA)-DRB1 gene polymorphism and environmental risk factors in gestational diabetes mellitus ( GDM ) pathogenesis.Methods Pregnant women who had prenatal cares in Obstetric Department , West China Second Hospital of Sichuan University were recruited from January 1st to December 31st in 2011.A prospective cohort study was conducted in the women who had a glucose challenge test ( GCT) or 75 g oral glucose tolerance test ( OGTT) during 24-28 gestational weeks.A total of 104 women diagnosed with GDM were randomly included in GDM group while another 103 normal women fell into the control group.The HLA-DRB1 polymorphism was detected by Polymerase Chain Reaction -Sequence Specific Primers ( PCR-SSP) method in both groups.The interactions between HLA-DRB1 polymorphism and environmental risk factors were analyzed based on the simple-case-study method.Results ( 1 ) There were 712 pregnant women with complete perinatal information during January 1st to December 31st, 2011, among whom 175 (24.6%) women were diagnosed with GDM.A logistic regression analysis showed that advanced maternal age (OR=1.081, 95%CI:1.027-1.138), imbalanced diet (OR=3.329, 95%CI:2.167 -5.116), high body mass index (BMI≥24.0 kg/m2) before pregnancy (OR=1.095, 95%CI:1.008 -1.190), HBsAg carrier status (OR=3.173, 95%CI:1.387-7.260) and family history of diabetes mellitus (DM) (OR=1.798, 95%CI:1.063 -3.041) were risk factors of GDM.(2) There were 49 HLA-DRB1 genotypes and 51 HLA-DRB1 genotypes in GDM group and the control group , respectively.We further compared the genotypes that occurred in over 3 cases in either group and found that HLA-DRB1*12,16 was only detected in 5 cases (5/103, 4.9%) in control group,and the difference was significant between the two groups (P=0.029).HLA-DRB1*11,16 and HLA-DRB1*09,09 were only detected in 4 cases (3.8%,4/104) and 5 cases (4.8%, 5/104) in GDM group respectively , but without significant differences between the two groups ( P >0.05 ).No significant difference was found in other genotype frequencies between the two groups ( P>0.05 ).( 3 ) Thirteen types of HLA-DRB1 allele were detected but no significant differences were observed in their frequencies between two groups ( P>0.05).(4) A positive interaction was detected between HLA-DRB1*07 polymorphism and advanced maternal ages (OR=5.952, 95%CI:1.314-26.970, P=0.022), while no interaction was found between HLA-DRB polymorphisms to other risk factors such as imbalanced diet , high body mass index ( BMI≥24.0 kg/m2 ) , HBsAg carrier status or DM family history.Conclusions Advanced maternal age, unbalanced diet, high body mass index (BMI≥24.0 kg/m2), HBsAg carrier status and DM family history are environmental risk factors of GDM in Chengdu.While HLA-DRB1*12,16 genotype may be a protective genotype for GDM.There is a positive interaction between HLA-DRB1*07 polymorphism and advanced maternal age which may play a critic role in GDM development.

Human Leukocyte Antigen-DRB1 Associations in Korean Juvenile Rheumatoid Arthritis

OBJECTIVE: The aim of this study is to investigate the association of different subgroups of juvenile rheumatoid arthritis (JRA) with human leukocyte antigen (HLA) class II DR alleles. METHODS: One hundred and nineteen Korean juvenile rheumatoid arthritis patients were classified as HLA-DRB1 allele. To assess the frequency, phenotype frequencies of all JRA cases and each subtypes were compared to those of 485 adult controls. RESULTS: HLA-DRB1*01 was associated with increased risk of JRA. Furthermore, DRB1*01 was associated with polyarticular JRA and pauciarticular JRA. The frequencies of DRB1*14 and DRB1*15 were higher in systemic JRA patients than the controls. CONCLUSION: The data of this study on Korean children with JRA suggests that HLA-DRB1*01 was associated with the susceptibility of JRA. The study should be extended to include larger numbers of patients.

Biomarcadores genéticos de los sistemas MHC/HLA-DRB1* y PTPN22 asociados a enfermedad reumática: artritis idiopática juvenil y artritis reumatoide de instalación temprana. Un enfoque analítico en un estudio piloto / Genetics Biomarckers off the MHC/HLA-DRB1* and PTPN 22 Systems Associated to Rheumatics diseases: idiopatic juvenile arthritis and rheumatoid of early installation. A descriptive approach in a pilot study

Objetivos: Identificar biomarcadores de susceptibilidad para AIJ poliarticular y AR de instalación temprana por estudio del polimorfismos de MHC/HLA-DRB1* y PTPN22. Materiales y métodos: Se realizó un estudio de casos y controles con una relación 1:2. Todos los sujetos de investigación y los controles provinieron de una corta anidada perteneciente a un proyecto institucional; 30 pacientes con AIJ y 30 con AR de instalación temprana. Como controles se estudiaron 60 individuos sanos. El ADN se obtuvo por salting out modificado. La tipificación de los alelos MHC/DRB1* se realizó por PCR-SSP y en el polimorfismo (C1858T) del sistema PTPN22 se utilizó PCR-RTq. Resultados: Para AIJ Poliarticular, el alelo DRB1*0404 se asoció con susceptibilidad (OR=10.82; p<0.05), en el grupo con AR de instalación temprana, DRB1*0101 se mostró como marcador de susceptibilidad (OR=4.04; p<0.05). Se destaca que el alelo HLA-DRB1*0701 aparece como marcador protector para ambas patologías (OR=0,15; p<0,05). El polimorfismo del SNP (C1858T) PTPN22 no se asoció con AIJ Poliarticular. En contraste, en AR de instalación temprana, el Alelo CC se asoció con protección p<0.05. En el mismo grupo, CT/TT se mostró como un marcador de susceptibilidad <0.05. El análisis de la secuencia aminoacídica 70QRRAA74 del epítope compartido se asoció con susceptibilidad para ambas entidades (p<0.05) y la secuencia 70DRRGQ74 con protección en ambos grupos de pacientes (p<0.05). Conclusión: Se destaca que en la asociación con la secuencia del epítope compartido, la ubicación del tipo de aminoácido y posición del mismo define probable asociación como marcador molecular de susceptibilidad en ambas entidades. Los polimorfismos compartidos sugieren un origen genético común para ambas entidades.

Objectives: To identify polymorphisms of MHCIHLA-DRB1* and PTPN22 systems as a genetic biomarker of susceptibility to JIA poliarticular and early installation RA. Material and methods; This was a pilot case control study with a relation of 1:2. Patients and control individuals involved in this study were selected from a nested cohort from an institutional previous RAIJIA project. The sample was represented by thirty patients with JIA and 30 diagnosed with early installation RA. Sixty unrelated healthy individuals were involved as a control DNA Isolation was obtained by a modified salting out technique. The oligotyping of the MHCIDRB1* alleles was performed by PCR-SSP and the typing of the PTPN22 polymorphism was done by RT-PCR. Results: The DRB1*0404 allele was associated with susceptibility to JIA(OR=10.82, P<0.05). In the early installation RA group the DRB1*0101 allele was showed as a marker of susceptibility to JIA patients (OR=4.04, P<0.05). It is noteworthy that the HLA-DRB1*0701 appears as a possible protective marker for both diseases (OR=015, p<0.05). The polymorphism of (C1858T)PTPN22 was not associated with poliarticular JIA. In contrast, in the early installation RA group of patients, the CC PTPN22 polymorphism was found to be as a protective marker (p<0.05). On the other hand, the amino acid sequence 70QRRAA74 of the share epitope was a marker for susceptibility to both entities (p<0.05) By contrast, the sequence 70DRRGQ74 of the same epitope was showed as a possible marker for protection on both entities (p<0.05.). Conclusion: The model that was used for searching association between the shared epitope -region 70-74 of the DRB1* alleles and these two entities showed the importance of the location and also the type of amino acid in those positions. The polymorphisms found as molecular markers of susceptibility for both entities suggested a common origin and could suggest its probable roll as a molecular marker of susceptibility.

Recurrent Insulin Autoimmune Syndrome Caused by alpha-Lipoic Acid in Type 2 Diabetes

Insulin autoimmune syndrome (IAS) is characterized by spontaneous hypoglycemia caused by insulin autoantibodies in the absence of exogenous insulin administration. Some drugs containing sulfhydryl compounds are known to initiate the onset of IAS. A 67-year-old female who had diabetes for 5 years visited the outpatient clinic at our institution due to diabetic peripheral polyneuropathy. She was prescribed alpha-lipoic acid (ALA), which contains two sulfur atoms. Two weeks later, she complained of recurrent hypoglycemic symptoms. We detected a high level of insulin and high titers of insulin autoantibodies. Her human leukocyte antigen (HLA) genotype included the DRB1*0406 allele, which indicates a high level of susceptibility to IAS. She was treated with prednisolone. After this episode, she experienced two more hypoglycemic events after taking ALA for diabetic neuropathy in other hospitals. As ALA can be used to treat diabetic peripheral polyneuropathy, physician discretion is advised based on the possibility of IAS due to ALA in diabetic patients.

Recurrent Insulin Autoimmune Syndrome Caused by alpha-Lipoic Acid in Type 2 Diabetes

Insulin autoimmune syndrome (IAS) is characterized by spontaneous hypoglycemia caused by insulin autoantibodies in the absence of exogenous insulin administration. Some drugs containing sulfhydryl compounds are known to initiate the onset of IAS. A 67-year-old female who had diabetes for 5 years visited the outpatient clinic at our institution due to diabetic peripheral polyneuropathy. She was prescribed alpha-lipoic acid (ALA), which contains two sulfur atoms. Two weeks later, she complained of recurrent hypoglycemic symptoms. We detected a high level of insulin and high titers of insulin autoantibodies. Her human leukocyte antigen (HLA) genotype included the DRB1*0406 allele, which indicates a high level of susceptibility to IAS. She was treated with prednisolone. After this episode, she experienced two more hypoglycemic events after taking ALA for diabetic neuropathy in other hospitals. As ALA can be used to treat diabetic peripheral polyneuropathy, physician discretion is advised based on the possibility of IAS due to ALA in diabetic patients.