Frequency Of DRB1 Research Articles

The frequency of HLA DRB1-DQB1 alleles in autoimmune type 1 diabetes with or without autoimmune thyroid disease

Introduction A common genetic susceptibility has long been reported between type 1 diabetes (T1D) and autoimmune thyroid disease (AITD). The HLA region became the first candidate to be studied for this association. The aim of this study was to identify the frequency of HLA DRB1-DQB1 alleles in T1D with or without AITD to clarify the susceptibility and the resistance of the two diseases. Participants and methods The study included 75 unrelated patients with T1D. About 50 T1D patients had no AITD (30 male and 20 female), 25 T1D patients had AITD (eight male and 17 female), and 40 healthy individuals served as the control group (17 male and 23 female) with mean ages of 40.6 ± 2.0, 40.5 ± 3.9, and 39 ± 4.3 years, respectively. The following investigations were performed on all participants: the thyroid profile (free T4, FT3, and thyroid-stimulating hormone), thyroid peroxidase antibodies (anti-TPO), and thyroglobulin antibodies (anti-TG). Autoantibodies against glutamic acid decarboxylase (anti-GAD) were determined. HLA-DRB1 and HLA-DQB1 alleles were determined by PCR-SSOP methods. Results HLA class II alleles showed an increased frequency of DRB1*0101, DRB1*0301, DRB1*0402, DRB1*0403, and total DR*04 alleles with DQB1*0201 and DQB1*0302 alleles both in T1D patients with AITD and in T1D patients without AITD in comparison with the control group. The frequency of the DRB1*0401 allele was significantly higher only in T1D patients without AITD in comparison with the control group. The frequency of the DQB1*0301 allele was significantly higher only in T1D patients with AITD in comparison with the control group. However, frequencies of DRB1*1001, DRB1*1101, and DRB1*1501 with DQB1*0404, DQB1*0601, DQB1*0602, and DQB1*0603 alleles were significantly lower both in T1D patients with AITD and in T1D patients without AITD in comparison with the control group. Conclusion Thus, DRB1*04, DRB1*0301, and DRB1*0101 and DQB1*0201 and DQB1*0302 confer susceptibility to both diseases. The frequency of DQB1*0301 confers susceptibility only to T1D patients with AITD, whereas DRB1*1001, DRB1*1101, and DRB1*1501 and DQB1*0404, DQB1*0601, DQB1*0602, and DQB1*0603 alleles confer protection.

High-resolution HLA analysis of primary and secondary Sjögren's syndrome: a common immunogenetic background in Mexican patients.

To compare the distribution of HLA-A, B, DRB1 and DQB1 alleles among Mexican patients with primary Sjögren Syndrome (pSS), secondary SS (sSS), connective tissue disease (CTD) without (w/o) SS and historical ethnically healthy controls. We included 28 pSS, 30 sSS, 96 CTD w/o SS patients and 234 controls. HLA-A, B, DRB1 and DQB1 were amplified and sequenced using the Allele SEQR Sequenced Based Typing Kits and analyzed on the ABI Prism*3130 DNA Analyzer using the Assign software. Gene frequencies were obtained by direct counting. Contingence tables of 2 × 2 were generated and analyzed by the Mantel-Haenzel χ (2) or Fisher's test (EPIINFO program). We reported odds ratios (OR) and corrected p values. SS patients showed increased frequencies of A*68:01 and DRB1*14:06 alleles when compared to CTD w/o SS (OR 4.43, 95 % CI 1.35-14.14, p = 0.007 and OR 14, 95 % CI 1.68-116, p = 0.001, respectively) and a higher prevalence of DRB1*01:01 (OR 5.9, 95 % CI 2.13-16.56, p = 0.003) and HLA-B*35:01 (OR 3.70, 95 % CI 1.92-7.12, p = 0.004) when compared with controls. pSS patients had a higher frequency of DRB1*14:06 allele than sSS (OR 16, 95 % CI 1.59-390, p = 0.001). Anti-Ro/SSA positivity was associated with B*51:01 (OR 10.11, 95 % CI 1.09-245, p = 0.02) and DRB1*03:01 alleles (OR 4.26, 95 % CI 1.01-18.89, p = 0.029), whereas the A*01:01 allele was associated with anti-La/SSB positivity (OR 4.75, 95 % CI 1.32-16.92, p = 0.003). In our population, the DRB1*14:06 allele was associated with primary and secondary SS implying that both varieties bear a similar immunogenetic background.

Association of polymorphisms of HLA-DRB1 gene with unexplained recurrent spontaneous abortion in ethnic Hans from Henan

To assess the association of polymorphisms of human leukocyte antigen DRB1 gene (HLA-DRB1) with susceptibility to unexplained recurrent spontaneous abortion (URSA). The HLA-DRB1 gene was typed with polymerase chain reaction-specific sequence primers (PCR-SSP) method in 200 couples with URSA and 200 couples with a normal pregnancy history. The frequencies of DRB1*09 and DRB1*13 alleles were significantly greater in the URSA group compared with the control group (14.50% vs. 9.50%, and 7.00% vs. 4.38%, both P<0.05), whilst the frequencies of DRB1*04 and DRB1*12 alleles were significantly lower (7.13% vs. 10.75%, and 8.63% vs. 14.38%, both P<0.05). For females from the URSA group, the frequency of DRB1*09 allele (14.00%) was significantly higher compared with the controls (9.25%) (P=0.036), whilst the frequency of DRB1*12(8.50%) allele was significantly lower (14.00%) (P=0.014). For males in the URSA group, the frequencies of DRB1*09 and DRB1*13 alleles were significantly higher than those of the controls (15.00% vs. 9.75%, and 9.25% vs. 4.00%, both P<0.05), whilst the frequencies of DRB1*04 and DRB1*12 alleles were significantly lower (5.75% vs. 12.25%, and 8.75% vs. 14.75%, P<0.05). The DRB1*09 and DRB1*13 alleles may contribute to the susceptibility of URSA, while DRB1*04 and DRB1*12 alleles may confer a protective effect factors. For females, however, no significant association of DRB1*13 and DRB1*04 alleles with URSA was found.

Changes in median ages at death from selected cancer types in relation to HLA-DRB1/DQB1.

The median ages at death from cancers between 1985 and 2005 were calculated to demonstrate that inherent anticancer mechanisms may be a common pathway for different cancers. Seventy-eight patients with gastric, liver and lung cancers, were recruited in the solid cancer group. The leukemia group consisted of 31 patients with three main types of leukemia. The controls were 100 healthy individuals. The samples were typed using an HLA-DR/DQ PCR-SSP typing kit. The results showed that the median ages at death from all causes were 64.7 years in 1985 and 70.1 years in 2005. The range of the median ages at death from all cancers was similar to the corresponding value for deaths attributed to all causes. The frequency of DRB1*03 was 9.6% in the solid cancer group and 3.0% in the control group (p<0.05). The frequency of DRB1*04 in the leukemia group were significantly lower than that of the control (p<0.05). DRB1*13 and DQB1*06 frequencies in the leukemia group were significantly higher than those of the controls (p<0.05). It is suggested that inherent anti-cancer mechanisms may be a common pathway for different cancers and are associated with the immune system and HLA.

Genetic and infectious profiles influence cerebrospinal fluid IgG abnormality in Japanese multiple sclerosis patients.

BackgroundAbnormal intrathecal synthesis of IgG, reflected by cerebrospinal fluid (CSF) oligoclonal IgG bands (OBs) and increased IgG index, is much less frequently observed in Japanese multiple sclerosis (MS) cohorts compared with Western cohorts. We aimed to clarify whether genetic and common infectious backgrounds influence CSF IgG abnormality in Japanese MS patients.MethodologyWe analyzed HLA-DRB1 alleles, and IgG antibodies against Chlamydia pneumoniae, Helicobacter pylori, Epstein-Barr virus nuclear antigen (EBNA), and varicella zoster virus (VZV) in 94 patients with MS and 367 unrelated healthy controls (HCs). We defined CSF IgG abnormality as the presence of CSF OBs and/or increased IgG index (>0.658).Principal FindingsCSF IgG abnormality was found in 59 of 94 (62.8%) MS patients. CSF IgG abnormality-positive patients had a significantly higher frequency of brain MRI lesions meeting the Barkhof criteria compared with abnormality-negative patients. Compared with HCs, CSF IgG abnormality-positive MS patients showed a significantly higher frequency of DRB1*1501, whereas CSF IgG abnormality-negative patients had a significantly higher frequency of DRB1*0405. CSF IgG abnormality-positive MS patients had a significantly higher frequency of anti-C. pneumoniae IgG antibodies compared with CSF IgG abnormality-negative MS patients, although there was no difference in the frequency of anti-C. pneumoniae IgG antibodies between HCs and total MS patients. Compared with HCs, anti-H. pylori IgG antibodies were detected significantly less frequently in the total MS patients, especially in CSF IgG abnormality-negative MS patients. The frequencies of antibodies against EBNA and VZV did not differ significantly among the groups.ConclusionsCSF IgG abnormality is associated with Western MS-like brain MRI features. DRB1*1501 and C. pneumoniae infection confer CSF IgG abnormality, while DRB1*0405 and H. pylori infection are positively and negatively associated with CSF IgG abnormality-negative MS, respectively, suggesting that genetic and environmental factors differentially contribute to MS susceptibility according to the CSF IgG abnormality status.

Allelic variation in HLA‐DRB1* loci in Syrian pemphigus vulgaris patients

Pemphigus vulgaris (PV) is known to be strongly associated with particular alleles of the human leukocyte antigen (HLA)-DRB1* loci. However, to date, the association of HLA with pemphigus has not been studied in a Syrian population. We aimed to study HLA-DRB1* loci variation in Syrian PV patients. We used a sequence-specific primer polymerase chain reaction method to define the allele type of the DRB1* loci in 91 patients with PV and 270 healthy control subjects. We noticed an increased frequency of HLA-DRB1*04 and DRB1*14 alleles in patients with PV compared with healthy control subjects (67.0% vs. 26.3%; odds ratio [OR] = 5.7, corrected P < 0.0001 for DRB1*04; 54.9% vs. 11.0%; OR = 9.5, corrected P < 0.0001 for DRB1*14). Among DRB1*04-positive PV patients, the DRB1*402 subtype was markedly increased compared with DRB1*04-positive healthy controls (84.3% vs. 26.7%; corrected P = 0.002), whereas the DRB1*0403 variant was represented more commonly in DRB1*04-positive healthy individuals than in DRB1*04-positive PV patients (45.0% vs. 1.6%; corrected P < 0.0001). In addition, the frequency of DRB1*11 was significantly decreased in PV patients compared with healthy controls (19.7% vs. 50.4%; OR = 0.25, corrected P < 0.0001). The occurrence of PV is positively associated with HLA-DRB1*14 and HLA-DRB1*0402 but negatively associated with HLA-DRB1*11 in the Syrian population.

Genetic Polymorphisms HLA Class II in SIRS and Sepsis in Children

Aims: The aim of this research was to investigate the genetically determined predisposition to develop SIRS and sepsis by analyzing human leukocyte antigen HLA class II genes. Study Design: children defined by the criteria for SIRS of Critical Care Medicine Consensus Conference were included into the study in a prospective manner. Place and Duration of Study: Riga Stradiņs University Laboratory of Clinical Immunology and Immunogenetic, Department of Pediatrics, Rīga Stradiņs University, and Children’s Clinical University Hospital, Latvia, between January 2008 and May 2009. Methodology: Samples from children with SIRS and sepsis were collected at the Children`s Clinical University Hospital of Latvia. During the study, 65 patients with SIRS were observed. In 12 cases among SIRS patients, sepsis was confirmed. DNA was separated from lymphocytes of peripheral blood. At the same time, 100 DNA samples Research Article British Journal of Medicine & Medical Research, 4(1): 149-160, 2014 150 from healthy children were analysed. HLA typing low-resolution for HLADRB1; DQB1; DQA1 was performed by polymerase chain reaction (PCR) with amplification with sequence-specific primers (SSP). PCR products were separated on 3% arose, the amplified bands were visualised. The frequency of alleles and genotypes were compared between the patients and the controls using chi-square test. P-value and odds ratio were calculated using EPI INFO software version 6 with 95 % confidence intervals and Fisher exact correction for small numbers. Results: The frequency of DRB1*07:01 allele was significantly increased in patients with SIRS (OR=8.71; 95% Cl = 2.8-26.8; p<0.0001) and patients with sepsis (OR=9 .70; 95% Cl = 2.3-42.2; p<0.005). In-group SIRS was significantly increased DQB1*03:02 (OR=2.19; 95% Cl = 1.1-4.8; p<0.049) and sepsis group DQB1*03:01 (OR=2.95; 95% Cl = 1.3-7.1; p<0.013) alleles also. But the frequency of DRB1*15:01 (OR=0.50; ; 95% Cl = 0.2-0.9; p<0.038) and DQB1*06:01, (OR=0.16; 95% Cl = 0.2-1.3; p<0.042) alleles was lower in all SIRS patients than in control group. In the distribution of HLA DRB1*/DQA1*/DQB1*, such haplotypes as DRB1*07:01/DQA1*02:01/DQB1*03:02, (OR=8.08; 95% Cl = 0.9-74.2; p<0.049); DRB1*07:01/DQA1*02:01/DQB1*05:01, (OR=8.08; 95% Cl = 0.9-74.2; p<0.049) and DRB1*04:01/DQA1*03:01/DQB1*02:01-2 (OR=5.10; 95% Cl = 0.9-27.3; p<0.049) in SIRS group were frequently detected. The haplotypes DRB1*07:01/DQA1*02:01/DQB1*03:01, (OR=33; 95% Cl = 0.9-27.3; p<0.004); DRB1*07:01/DQA1*03:01/DQB1*03:01; (OR=19.80; 95% Cl = 0.9-27.3; p<0.029) and DRB1*04:01/DQA1*02:01/DQB1*03:01, (OR=19.80; 95% Cl = 0.9-27.3; p<0.03) were frequently found in septic group patients. Conclusion: Our pilot data shows that the susceptibility markers HLA-DRB1*07:01/ DQA1*02:01/ DQB1*03:01, in sepsis patients are partly consistent with literature data. The number of patients in the study is relatively small. In order to increase statistical significance of results and to prove current findings, it is important to continue the study.

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.

HLA-DRB1 and HLA-DQB1 allele associations in an Albanian patient population with rheumatoid arthritis: correlations with the specific autoantibody markers and inter-population DRB1 allele frequency variability

The prevalence of rheumatoid arthritis 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. In this context, we studied the HLA-DRB1 and HLA-DQB1 first-level allele frequencies in 100 Albanian patients with rheumatoid arthritis (RA), and taking into account their rheumatoid factor (RF) and anticitrullinated peptide antibodies (ACPA) serologic subgroups, we compared them with the respective frequencies in a population of 191 Albanian individuals without known pathology. No differences were found between the controls and the RA patient group as a whole, but three statistically significant differences were found: an increase in DRB1*04 among ACPA+, RF+ and ACPA+/RF+ patients, a significant decrease in DRB1*11 among ACPA+/RF+ and also a decrease in DRB1*13 among RF+ patient subgroups. Comparing allele frequencies of putatively associated RA alleles in different European populations revealed a significant negative correlation between the RA predisposing DRB1*04 and protective DRB1*11 allele frequencies. A statistically significant correlation was also found between RA prevalence rates and DRB1*04 as well as DRB1*11 frequencies. The relatively low frequencies of DRB1*04 and high DRB1*11 in the Albanian population might explain the rather low positivity rate of ACPA and RF antibodies among the Albanian RA patients. These specific association patterns suggest that this first study of RA in an Albanian population should be followed up to include second level or higher definition of HLA alleles and to compare RA patterns among European populations.

Genetic susceptibility to multicase hypersensitivity pneumonitis is associated with the TNF-238 GG genotype of the promoter region and HLA-DRB1*04 bearing HLA haplotypes

Hypersensitivity Pneumonitis (HP) is a lung inflammatory disorder caused by inhalation of organic particles by a susceptible host. Since only a small proportion of individuals exposed to HP-related antigens develop the disease, a genetic predisposition is largely suspected. However, studies regarding genetic susceptibility in this disease are scanty. We have previously found evidence supporting increased risk associated to the major histocompatibility complex (MHC) in sporadic HP. In the present study, we conducted a family-based research that includes nine multicase families with at least two related HP patients (RHP). We evaluated 19 RHP individuals, 25 additional healthy first-degree relatives (REA) and 246 healthy unrelated individuals (HUI). HLA class II typing (DRB1/3/4/5, DQA1, DQB1, DPA1, DPB1, DMA and DMB), and -863, -308 and -238 polymorphisms in the promoter region of TNF-α were performed by PCR based methods. We identified an increased frequency of HLA-DRB1*04:07, DRB1*04:05, DRB1*11:01 and DRB1*13:01 alleles in RHP individuals compared to healthy controls (p<0.05). A significant higher frequency of DRB1*04:07-DQB1*03:02, DRB1*04:05-DQB1*03:02, and DRB1*04:03-DQB1*03:02 haplotypes was also detected in the group of patients. Likewise, TNF-238 GG genotype was more frequent in the RHP group as compared to REA (p=0.01, OR=7.2). Finally, the combination of HLA-DRB1*04 alleles and TNF-238 GG was significantly increased in the RHP group (p=0.01, OR=6.93). These findings indicate that genes located within the MHC region confer susceptibility to familial HP in Mexicans.

164-P: HLA DQB1 06:09 SIGNIFICANTLY INCREASES THE RISK OF MULTIPLE SCLEROSIS AMONGST PARSIS (ZOROASTRIANS) OF INDIA

The frequency of Multiple Sclerosis (MS) varies worldwide. Zoroastrians (Parsis) of Mumbai, India comprise a tiny inbred group who have shown a significantly higher prevalence of MS. DNA typing of HLA Class II DRB1 and DQB1 alleles was performed on 13 Parsi patients. DNA was extracted from blood samples of 13 MS Parsi patients (remitting relapsing) and 50 healthy Parsi controls. Low and high resolution HLA-DRB1 and DQB1 molecular typing was performed by polymerase chain reaction using sequence specific primers (PCR-SSP) (Olerup SSP, Qiagen). A statistically significant increase in HLA-DRB1∗15 xx (23% vs. 8%) and HLA-DQB1∗06 xx (26.9% vs 8%,) was detected in Parsi patients as compared to controls. High resolution typing of HLA-DQB1∗06 xx amongst them showed a significant increase in DQB1∗06:09 (11.53% vs. 2%) OR = 7.2; Chi square = 2.86; p value 0.05, CI (0.82-73.29).[ Table 1 ] Dean and Wadia studied MS patients amongst Asian immigrants in England. Five Parsis were found with definite MS in a community of 5000, as compared to 23 amongst 383,000 ethnic Indian immigrants. It has been of some concern that our genetic analysis is in a small number of patients, but such is the cohort available from this tiny community, which is now spread worldwide. Earlier clinical data has shown small affected populations can yield valuable information that may reflect on broader issues of genetic susceptibility. So a higher frequency of DRB1∗15 and DQB1∗06 in MS patients with a statistically significant increase in the DQB1∗06:09 allele is detected.

The association of HLA-DRB1 alleles and drug use with HIV infection in a Chinese Han Cohort

ObjectiveTo investigate the relationship between the polymorphism of human leukocyte antigen (HLA)-DRB1 and the susceptibility and repellency of drug use combined with HIV infection in Chinese. MethodsA total of 213 unrelated healthy people, 41 HIV-infected drug users, 24 HIV-uninfected drug users, and 64 HIV-infected non-drug users were recruited. Their HLA-DRB1 allele frequencies were analyzed by PCR-SSP and allele distribution was analyzed. ResultsCompared with healthy controls, in drug users, the frequencies of HLA-DRB1 *0401-041, *1001 were significantly higher; in HIV-infected patients, the frequencies of HLA-DRB1 *0101-0103, *0401-0411, *1001 were significantly higher, while the frequencies of DRB1 *1501-1502, *1101-1105, *1301-1302, DRB4, DRB5 were significantly lower; in HIV-infected drug users, the frequencies of HLA-DRB1 *0101-0103, *0401-0411, *0801-0806, *1001, *1401/1404/1405 were significantly higher, while the frequencies of DRB1 *1301/1302, 1501-1502, DRB5 were significantly lower. ConclusionThere is close relationship between the polymorphism of HLA-DRB1 alleles and drug use with HIV infection, which plays an important role in elucidating the pathogenesis and providing the basis for therapeutics and prophylaxis of patients with drug use and HIV infection.

Association of HLA alleles and haplotypes with vitiligo in Moroccan patients: a case–control study

The aim of this study was to identify HLA class II alleles that may be involved in vitiligo genetic susceptibility in the Moroccan population and to determine susceptible and protective HLA alleles/haplotypes in vitiligo. One-hundred unrelated vitiligo patients and 300 healthy unrelated controls were studied for HLA class II alleles by polymerase chain reaction-sequence-specific primers. The phenotypic frequency of DRB1*07 (OR=2.23, p c=0.014) was significantly higher, while that of DRB1*03 (OR=0.40, p c=0.014) was significantly lower in patients than in controls. Haplotype DRB1*07-DQB1*02 (OR=2.25, p c=0.024) was positively associated with vitiligo patients, while haplotype DRB1*03-DQB1*02 (OR=0.35, p c=0.012) was negatively associated with this group. Vitiligo patients with positive family history and negative anti-thyroid peroxidase antibody (anti-TPO) have an extremely high phenotype frequency of DRB1*07-DQB1*02 haplotype (OR=2.91, p c=0.048 and OR=2.62, p c=0.00475, respectively). DRB1*03-DQB1*02 (OR=0.32, p c=0.048 and OR=0.38, p c=0.048, respectively) was negatively associated with patients without a family history and negative anti-TPO. This study demonstrated the positive association of HLA class II alleles and haplotypes with vitiligo in the Moroccan population. There may be differences in HLA haplotypes distribution in patients according to family history and anti-TPO profile.

Distinct genetic profiles between Japanese multiple sclerosis patients with and without Barkhof brain lesions

AbstractObjectivesThe frequency of brain lesions that fulfil the Barkhof criteria (Barkhof brain lesions) is low in Asian patients with multiple sclerosis (MS). Several genes are associated with MS in the Japanese, but their influence on brain lesion development is unknown. Here, we clarified the genetic profiles of Barkhof brain lesion‐positive and ‐negative MS in the Japanese.MethodsWe genotyped the HLA‐DRB1 and ‐DPB1 alleles, the NOTCH4 missense mutation rs422951, and the IL‐7RA single nucleotide polymorphism rs6897932 in 123 non‐neuromyelitis optica/neuromyelitis optica spectrum disorder MS patients and 367 healthy controls by annealing of sequence‐specific oligonucleotide probes to polymerase chain reaction‐amplified genomic DNA (for the HLA alleles), DNA sequencing (for rs422951), and real‐time polymerase chain reaction using TaqMan genotyping assays (for rs6897932).ResultsCompared with the healthy controls, the frequency of DRB1*0405 was significantly higher in the Barkhof brain lesion‐negative group, that of DPB1*0301 was significantly higher in the Barkhof brain lesion‐positive group, and those of DRB1*0901 and DPB1*0401 were significantly lower in the Barkhof brain lesion‐positive group. The frequency of NOTCH4 rs422951 G allele carriers was significantly lower in both groups compared with the healthy controls, whereas the frequency of the IL‐7RA rs6897932 CC genotype was significantly higher in the Barkhof brain lesion‐positive group. Haplotype analyses identified one susceptibility and three resistance haplotypes for Barkhof brain lesion‐positive MS, and two susceptibility and three resistance haplotypes for Barkhof brain lesion‐negative MS.ConclusionsThe genetic profiles of Japanese MS patients are distinct according to the presence or absence of Barkhof brain lesions.

Associations of HLA-DRB1 and -DQB1 alleles with severe recurrent respiratory papillomatosis in Korean patients

Recurrent respiratory papillomatosis (RRP) is characterized by frequent recurrences of papilloma of the larynx with significant morbidity. It is caused by human papillomavirus (HPV) types 6 and 11. Some associations of HLA genes with RRP have been reported, mainly in Caucasians. We performed HLA class II (DRB1 and DQB1) genotyping using Dynal RELI™ HLA-DRB1 SSO kit and PCR-single strand conformation polymorphism on 22 Korean patients with severe RRP and 207 healthy controls. The gene frequencies of HLA-DRB1*11:01 (18.2% vs 3.6%, p=0.0006, pc=0.02, odds ratio [OR]=5.9) and DQB1*03:01 (36.4% vs 14.5%, p=0.0009, pc=0.01, OR=3.4) and the haplotype frequency of DRB1*11:01-DQB1*03:01 (15.9% vs 3.6%, p=0.003, OR=5.0) was higher in RRP patients than controls. DRB1*11:01 and DRB1*11:01-DQB1*03:01 haplotype were strongly associated with disease susceptibility to severe RRP in Koreans.

Association between HLA-DQB1*03:01 and Bullous pemphigoid in Iranian patients.

A common Human Leukocyte Antigen (HLA) class II allele, DQβ1*03:01, seems to be associated with Bullous pemphigoid (BP) in Caucasians whereas previous studies in other ethnic groups showed other HLA class II alleles as genetic predisposing factors for BP. To investigate the association of HLA class II alleles and haplotypes with BP in Iranian population. Fifty patients with Bullous pemphigoid and 180 geographically matched, healthy individuals as control group enrolled into this study. HLA typing of class II (DR and DQ alleles) was carried out using polymerase chain reaction based on sequence-specific primers method. Class II DQA1 and DQB1 typing showed a significantly higher frequency of HLA-DQA1*05:01 (45% vs. 33%, p=0.03), HLA-DQB1*03:01 (36% vs. 23.6%, p=0.02) and HLA-DQB1*04:01 (4% vs. 1.6%, p=0.04) in the BP patients compared with controls. For DRB1 allele frequencies, there were no significant disease associations. The frequency of DRB1*08:01/DQA1*05:01/DQB1*03:01 (3% vs. 0%, p=0.02) haplotype showed an increase among patients compared with controls. Our data suggest that Iranian patients with BP present the same genetic predisposition linked to HLA-DQB1*03:01 previously reported in Caucasians.

Effect of human leukocyte antigen class II genes on Hashimoto’s thyroiditis requiring replacement therapy with levothyroxine in the Japanese population

Contribution of the human leukocyte antigen (HLA) subtype to Hashimoto's thyroiditis (HT) that requires replacement therapy with levothyroxine remains unclear in the Japanese population. The frequencies of HLA DR-DQ haplotypes were compared between patients with HT requiring levothyroxine replacement therapy and the control individuals. We studied 82 patients with HT requiring levothyroxine replacement therapy. The frequencies of DRB1*08:03-DQB1*06:01 and DRB1*09:01-DQB1*03:03 haplotypes were significantly higher in HT patients, whereas those of DRB1*13:02-DQB1*06:04 and DRB1*15:01-DQB1*06:02 haplotypes were significantly lower in these patients than in the controls. Deduced from known linkage disequilibria, DRB1*13:02-DQB1*06:04 and DRB1*15:01-DQB1*06:02 haplotypes share the same DQA1*01:02 allele. Since DQB1*06:02 and DQB1*06:04 molecules differ in the beta chain by 7 residues, these DQB1 genes are very similar. The DQA1*01:02-DQB1*06 (DQB1*06:02 or DQB1*06:04) haplotype might play a pivotal role in the resistance to HT.

Difference inDRB1* gene polymorphisms between Han and Uyghur ulcerative colitis patients in China

To evaluate the association between HLA-DRB1 alleles and Han and Uyghur ulcerative colitis (UC) patients residing in the Xinjiang Uyghur Autonomous Region of China. In this study, 102 UC patients (53 Han including 22 men and 31 women, and 49 Uyghur patients including 25 men and 24 women; aged 48.07 ± 15.83 years) and 310 age- and sex-matched healthy controls were enrolled in the Department of Gastroenterology, Xinjiang People's Hospital of China from January 2010 to May 2011. UC was diagnosed based on the clinical, endoscopic and histological findings following Lennard-Jones criteria. Blood samples were collected and genomic DNA was extracted by routine laboratory methods, and both polymerase chain reaction and gene sequencing were used to identify HLA-DRB1 allele variants. The potential association between genetic variation and UC in Han and Uyghur patients was examined. There were no statistical differences in HLA-DRB1 allele frequencies in Han UC patients. There was no significant difference in the sex ratio between the controls and UC patients (P = 0.740). In Han patients with UC (n = 53), HLA-DRB1 *03, *13 allele frequencies were lower than in healthy controls (n = 161), but not statistically significant, and HLA-DRB1*04*11*14 allele frequencies were higher than in healthy controls, but without statistical significance. Differences between Uyghur UC patients and the control group were observed for HLA-DRB1*04 and HLA-DRB1*13, both showed a greater frequency in UC patients (10.21% vs 2.69%, P = 0.043; 14.29% vs 4.03%, P = 0.019). HLA-DRB1*14 also showed a greater frequency in UC patients (14.29% vs 2.69%, P = 0.006). The frequencies of DRB1*04, *13*14 alleles were increased in Uyghur UC patients compared with normal controls. The frequency of DRB1 * 08 was decreased in Uyghur UC patients compared with normal controls. HLA-DRB1 alleles showed no association with UC in Han patients. There were no statistical differences in HLA-DRB1 allele frequencies in Han UC patients. The frequencies of DRB1*04, *13*14 alleles were increased in Uyghur UC patients compared with normal controls. The frequency of DRB1*08 was decreased in Uyghur UC patients compared with normal controls. Polymorphism of the HLA-DRB1 gene may contribute to the clinical heterogeneity of UC between Han and Uyghur UC patients in China. HLA-DRB1*04*13*14 and DRB1*08 may contribute to the clinical heterogeneity of UC between Han and Uyghur UC patients.

Evaluation of a histocompatibility antigen related to hepatitis B virus in patients with hepatocellular carcinoma in the western Brazilian Amazon

Hepatocellular carcinoma is an infection of variable incidence that can be caused by hepatitis B virus (HBV), which is endemic in the Amazon region. The diagnosis of HBV can be performed through the use of serum markers such as the hepatitis B surface antigen. The chronic HBV can cause mutagenesis and carcinogenesis, being the susceptibility of infection due to allele human leukocyte antigen (HLA). Thus, we evaluated the clinical, molecular and laboratory profile (histocompatibility complex) of HBV in 22 patients with hepatocellular carcinoma in Amazonia, including 18 males and 4 females, using a blood sample for generic HLA class II. The results showed increased frequency of disease evolution in adults between 25 and 64 years old, who comprised 19 of the 22 patients studied. Most patients (16/22) presented high levels of alpha-fetoprotein and transaminases (14/22). The most common HLA alleles were DRB1 04 (8/44), DRB1 08 (9/44), DRB 03 (16/44), and DQB1 04 (9/44). When we compared specific phenotype frequencies of HLA-DRB1 between patients and controls, we found that patients had a significantly higher frequency of allele DRB1 08 and a significantly lower frequency of DRB1 07 and DRB1 12 compared to previous studies on Asian and Amazonian populations suggesting ethnic differences. We suggest that alleles HLA-DRB 08, HLA-DRB 03 and HLA-DQB1 04 may be risk factors for hepatocellular carcinoma in Amazon.

Altered expressions of peripheral CD11c, CD80, CD83 markers and associations of HLA class II allele and haplotypes in self-limiting Hepatitis E infection

Hepatitis E virus (HEV), the major cause of self limiting viral hepatitis, is associated with a robust humoral, moderate CD4 T cell and CTL response. However, key questions like the probable involvement of HLA class II alleles and peripheral DCs/monocytes in regulating the innate and adaptive immune responses in Hepatitis E remain unanswered. One eighty four self- limiting Hepatitis E patients and 283 anti-HEV negative controls from Western India were studied for the distribution of HLA class II alleles and the frequencies of peripheral CD80, CD83, CD86, HLA-DR and CD11c by PCR SSP method and flow cytometry respectively. Frequency of DRB1(∗)11 allele group was significantly low while haplotypes DRB1(∗)15/DQB1(∗)06 and DRB1(∗)10/DQB1(∗)05 were significantly high in the patient population. CD11c, CD80 and CD83 expressions were high in the patient groups. CD11c expression was positively associated with viral load. CD86 expression was significantly low in the patients having DQB1(∗)06 allele. Association of HLA-DRB1(∗)11 and the emergence of DRB1(∗)15/DQB1(∗)06 and DRB1(∗)10/DQB1(∗)05 as susceptible haplotypes towards HEV infection is being reported for the first time. Positive correlation of CD11c with HEV viral load suggested that increased frequencies of the same might be associated with HEV replication.