scholarly journals Shared HLA Class II in Six Autoimmune Diseases in Latin America: A Meta-Analysis

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Paola Cruz-Tapias ◽  
Oscar M. Pérez-Fernández ◽  
Adriana Rojas-Villarraga ◽  
Alberto Rodríguez-Rodríguez ◽  
María-Teresa Arango ◽  
...  

The prevalence and genetic susceptibility of autoimmune diseases (ADs) may vary depending on latitudinal gradient and ethnicity. The aims of this study were to identify common human leukocyte antigen (HLA) class II alleles that contribute to susceptibility to six ADs in Latin Americans through a meta-analysis and to review additional clinical, immunological, and genetic characteristics of those ADs sharing HLA alleles. DRB1∗03:01 (OR: 4.04; 95%CI: 1.41–11.53) was found to be a risk factor for systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), and type 1 diabetes mellitus (T1D). DRB1∗04:05 (OR: 4.64; 95%CI: 2.14–10.05) influences autoimmune hepatitis (AIH), rheumatoid arthritis (RA), and T1D; DRB1∗04:01 (OR: 3.86; 95%CI: 2.32–6.42) is a susceptibility factor for RA and T1D. Opposite associations were found between multiple sclerosis (MS) and T1D. DQB1∗06:02 and DRB1∗15 alleles were risk factors for MS but protective factors for T1D. Likewise, DQB1∗06:03 allele was a risk factor for AIH but a protective one for T1D. Several common autoantibodies and clinical associations as well as additional shared genes have been reported in these ADs, which are reviewed herein. These results indicate that in Latin Americans ADs share major loci and immune characteristics.

2000 ◽  
Vol 85 (3) ◽  
pp. 1176-1179 ◽  
Author(s):  
Yoshikuni Sawai ◽  
Leslie J. DeGroot

Abstract Abstract There are many reports that Graves’ disease (GD) is associated with certain human leukocyte antigen (HLA) molecules, in particular DR3. Here we examined the characteristics of binding of human TSH receptor (TSHR) peptides to this disease-associated HLA class II molecule. DR3 molecules bind TSHR immuonodominant peptide epitopes with intermediate affinity. On the contrary, DR3 binds nonimmunogenic peptides either with poor affinity or not at all, with one exceptional peptide that has extremely high affinity. These results suggest that susceptibility to GD associated with inheritance of a specific HLA class II gene is due to the influence of the HLA molecule-TSHR peptide complex on the T cell repertoire.


2021 ◽  
Author(s):  
Anja Panhuber ◽  
Giovanni Lamorte ◽  
Veronica Bruno ◽  
Hakan Cetin ◽  
Wolfgang Bauer ◽  
...  

Abstract Autoimmune diseases caused by pathogenic IgG4 subclass autoantibodies (IgG4-AID) include diseases like MuSK myasthenia gravis, pemphigus vulgaris or thrombotic thrombocytopenic purpura. Their etiology is still unknown. Polymorphisms in the human leukocyte antigen (HLA) gene locus, particularly in HLA-DRB1, are known genetic susceptibility factors for autoimmune diseases. We hypothesized a similar role for HLA polymorphisms in IgG4-AID and conducted a systematic review and meta-analysis with case-control studies on IgG4-AID based on MOOSE/ HuGENet guidelines. Genotype (G) and allele (A) frequencies of HLA-DQB1*05 (G: OR 3.8; 95% CI 2.44-5.9; p < 0.00001; A: OR 2.54; 95% CI 1.82-3.55; p < 0.00001) and HLA-DRB1*14 (G: OR 4.31; 95% CI 2.82-6.59; p < 0.00001; A: OR 4.78; 95% CI 3.52-6.49; p < 0.00001) and the HLA-DRB1*14-DQB1*05 haplotype (OR 6.3; 95% CI 3.28-12.09; p < 0.00001 / OR 4.98; 95% CI 3.8-6.53; p < 0.00001) were increased while HLA-DRB1*13 (G: OR 0.48; 95% CI 0.34-0.68; p < 0.0001; A: OR 0.46; 95% CI 0.34-0.62; p < 0.00001) was decreased in IgG4-AID patients. In conclusion, the HLA-DQB1*05, HLA-DRB1*14 alleles and the HLA-DQB1*05-DRB1*14 haplotype could be genetic risk factors that predispose for the production of pathogenic IgG4 autoantibodies and the HLA-DRB1*13 allele may protect from IgG4 autoimmunity.


2005 ◽  
Vol 12 (1) ◽  
pp. 213-217 ◽  
Author(s):  
Ayesha A. Motala ◽  
Marc Busson ◽  
Einas M. Al-Harbi ◽  
Manal A. A. Khuzam ◽  
Emtiaz M. D. Al-Omari ◽  
...  

ABSTRACT Whereas the genetic risk for type 1 diabetes is linked to human leukocyte antigen (HLA) class II genes, the HLA association in type 2 (non-insulin-dependent) diabetes is less clear. The association between HLA class II genotypes and type 2 diabetes was examined in adult Bahrainis, an Arab population with a high prevalence of type 2 diabetes. HLA-DRB1* and -DQB1* genotyping of 86 unrelated type 2 diabetes patients (age, 51.6 ± 8.2 years; mean duration of diabetes, 7.7 ± 7.1 years) who had a strong family history of diabetes (52 of 72 versus 0 of 89 for controls, P < 0.001) and 89 healthy subjects was done by PCR-sequence-specific priming. DRB1*040101 (0.1221 versus 0.0562, P = 0.019) and DRB1*070101 (0.2151 versus 0.0843, P < 0.001) were positively associated, while DRB1*110101 (0.0698 versus 0.1461, P = 0.014) and DRB1*160101 (0.0640 versus 0.1236, P = 0.038) were negatively associated with type 2 diabetes. DRB1*040101-DQB1*0302 (0.069 versus 0.0007; P = 0.004), DRB1*070101-DQB1*0201 (0.178 versus 0.0761, P = 0.007), DRB1*070101-DQB1*050101 (0.125 versus 0.0310, P = 0.002), and DRB1*150101-DQB1*060101 (0.0756 versus 0.0281, P = 0.008) were more prevalent among patients, while DRB1*160101-DQB1*050101 (0.0702 versus 0.0349, P = 0.05) was more prevalent among controls, conferring disease susceptibility or protection, respectively. In Bahrainis with type 2 diabetes, there is a significant association with select HLA class II genotypes, which were distinct from those in type 1 diabetes.


2016 ◽  
Vol 26 (8) ◽  
pp. 1503-1509 ◽  
Author(s):  
Sanne Samuels ◽  
Vivian M. Spaans ◽  
Michelle Osse ◽  
Lex A.W. Peters ◽  
Gemma G. Kenter ◽  
...  

ObjectivesHuman leukocyte antigen (HLA) class II antigens are expressed on antigen-presenting cells, that is, macrophages, dendritic cells, and B lymphocytes. Under the influence of IFN-γ, HLA class II molecules can also be expressed on T lymphocytes, epithelial and endothelial cells. In addition, HLA class II antigens can be expressed in a variety of malignancies; however, the link with prognosis and ultimately patient survival is controversial.MethodsThe pattern of HLA-DRA expression in cervical carcinoma was studied using immunohistochemistry. In total, 124 cervical carcinomas were examined, of which 60 (48.4%) were squamous cell carcinomas and 64 (51.6%) were adenocarcinomas.ResultsIn squamous cell carcinoma, HLA-DRA was expressed in 41 (68.3%) of 60 tumors, whereas in adenocarcinoma, HLA-DRA was expressed in 60 (93.8%) of 64 tumors (P< 0.001). In adenocarcinoma, HLA-DRA expression was associated with an increased disease-free survival (211.0 ± 13.0 vs 53.3 ± 30.5 months;P= 0.004) and disease-specific survival (226.45 ± 11.5 vs 75.8 ± 27.6 months;P= 0.002).ConclusionsUpregulation of HLA-DRA is significantly related to an increased disease-free and disease-specific survival in cervical adenocarcinoma. These data warrant further analysis of the functional role of HLA-DRA in these tumors.


Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5833
Author(s):  
Geok Wee Tan ◽  
Peijia Jiang ◽  
Ilja M. Nolte ◽  
Kushi Kushekhar ◽  
Rianne N. Veenstra ◽  
...  

Several human leukocyte antigen (HLA) alleles are strongly associated with susceptibility to classic Hodgkin lymphoma (cHL), also in subgroups stratified for presence of the Epstein–Barr virus (EBV). We tested the hypothesis that the pressure on cHL tumour cells to lose HLA expression is associated with HLA susceptibility alleles. A meta-analysis was carried out to identify consistent protective and risk HLA alleles in a combined cohort of 839 cHL patients from the Netherlands and the United Kingdom. Tumour cell HLA expression was studied in 338 cHL cases from these two cohorts and correlated to the presence of specific susceptibility HLA alleles. Carriers of the HLA-DRB1*07 protective allele frequently lost HLA class II expression in cHL overall. Patients carrying the HLA-DRB1*15/16 (DR2) risk allele retained HLA class II expression in EBV− cHL and patients with the HLA-B*37 risk allele retained HLA class I expression more frequently than non-carriers in EBV+ cHL. The other susceptibility alleles showed no significant differences in expression. Thus, HLA expression by tumour cells is associated with a subset of the protective and risk alleles. This strongly suggests that HLA associations in cHL are related to peptide binding capacities of specific HLA alleles.


2020 ◽  
Vol 17 (1) ◽  
pp. 7-10
Author(s):  
Seyyed Amir Yasin Ahmadi ◽  
Reza Mohammadrezaei-Khorramabadi ◽  
Saber Abbaszadeh ◽  
Jafar Rezaian ◽  
Farhad Shahsavar

Previously, the association of human leukocyte antigen (HLA)-B27 with ankylosing spondylitis has been investigated as original and meta-analysis studies. However, the association of HLA-B27 with rheumatoid arthritis is not currently investigated as a meta-analysis. Hence, in this letter, a brief meta-analysis on this association will be performed. Although there were some studies on the association of RA and HLA-B27, however, there was not a pooled odds ratio reported in textbooks. Based on this brief metaanalysis, number 2.687 can be reported as the odds ratio of this association. It shows that this association is neither sensitive nor specific, but can be an idea for pharmacogenomics and personalized medicine as a potential risk factor. Such other associations should be reported numerically and updated in textbooks.


2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Tao Xu ◽  
Meiqun Sun ◽  
Hongtao Wang

Hepatitis B virus (HBV) infection is the predominant risk factor for chronic hepatitis B (CHB). The association between HBV infection and human leukocyte antigen- (HLA-) DQ polymorphism (rs2856718 and rs7453920) has been demonstrated in other studies; however, the results were controversial or inconclusive. Therefore, to derive a more precise estimation of the association, a meta-analysis was performed. Crude odds ratios (ORs) and their 95% confidence intervals (CIs) were used to assess the strength of association between HLA-DQ polymorphism (rs2856718 and rs7453920) and HBV infection risk. A total of 11 articles were used to evaluate the effect of the two polymorphisms on risk of HBV infection. The pooled data showed that HLA-DQ rs2856718-G polymorphism showed protection against HBV infection, and rs2856718-A was a risk factor for chronic HBV infection. The pooled risk estimates indicated that HLA-DQ rs7453920-A polymorphism was associated with decreased risk of HBV infection, and rs7453920-G serves as a risk factor in HBV infection. However, these stratified analyses were lacking credibility due to the limitation of correlational study numbers; further investigation on a large population and different ethnicities is warranted.


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