Association of HLA Class II Alleles with Outcome of Hepatitis C Virus Infection: A Systematic Review and Meta-Analysis

Context: Hepatitis C Virus (HCV) infection is a major cause of chronic cirrhosis and hepatocellular carcinoma. Approximately 30% of infected persons with HCV spontaneously clear the viral infection; but, some of the remaining patients develop chronic HCV. Studies show that HLA molecules play an important role in the outcome of HCV infection by influencing the efficiency of the antiviral immune response to HCV infection. It is now known that polymorphisms in HLA loci are associated with HCV susceptibility or clearance. The purpose of the present study was to systematically review the studies that reported the association of HLA class II alleles (HLA-DQ and HLA-DR) with the outcome of HCV infection. Evidence Acquisition: Studies were identified by searching electronic databases, including PubMed and Scopus. A total of 12,265 relevant studies were identified by the electronic search, of which a total of 19 eligible papers were identified that were meta-analyzed for the association between HLA class II alleles and the outcome of HCV infection. Results: Subjects carrying HLA-DQB1*0301, HLA-DQB1*0501, HLA-DRB1*1303, HLA-DRB1*1201, HLA-DRB1*0401, HLA-DRB1*0101, and HLA-DRB1*1101 alleles were significantly associated with higher spontaneous clearance of HCV infection. Conclusions: The data from the current study confirm that several polymorphisms in HLA-DQ and HLA-DR loci are correlated with the clearance of HCV infection. Identifying these polymorphisms may contribute to a better understanding of immune mechanisms of HCV clearance or persistence.

HLA Does Not Impact on Short-Medium-Term Antibody Response to Preventive Anti-SARS-Cov-2 Vaccine

The response to anti-SARS-Cov-2 preventive vaccine shows high interpersonal variability at short and medium term. One of the explanations might be the individual HLA allelic variants. Indeed, B cell response is stimulated and sustained by CD4+ T helper cells activated by antigens presented by HLA-class II alleles on antigen-presenting cells (APCs). The impact of the number of antigens binding to HLA class-II alleles on the antibody response to the COVID vaccine has been assessed in a cohort of 56 healthcare workers who received the full schedule of the Pfizer-BioNTech BNT162b2 vaccine. Such vaccine is based on the entire spike protein of the SARS-CoV-2. Ab titers have been evaluated 2 weeks after the first dose as well as 2 weeks and 4 months after the boosting dose. HLA-DRB1 and DBQ1 for each of the vaccinees have been assessed, and strong binders have been predicted. The analysis showed no significant correlation between the short-medium-term Ab titers and the number of strong binders (SB) for each individual. These results indicate that levels of Ab response to the spike glycoprotein is not dependent on HLA class II allele, suggesting an equivalent efficacy at global level of the currently used vaccines. Furthermore, the pattern of persistence in Ab titer does not correlate with specific alleles or with the number of SBs.

Association of HLA Class II Alleles with Disease Severity and Treatment Response in Iranian Patients with Myasthenia Gravis

Myasthenia gravis is an autoimmune neuromuscular disease with a multifactorial etiology. A major part of the genetic susceptibility belongs to the HLA encoding genes. In this study, we investigated the role of HLA class II polymorphism in disease severity, and treatment response. In our 146 patients, 15 DRB1, 7 DQA1, and 9 DQB1 alleles, and 19 haplotypes were found. Adjusted p-values did not show any significant associations between these loci, disease severity and treatment outcome. Further studies in different populations with a larger number of patients are needed to determine the exact contribution of HLA class II alleles to MG prognosis.

Human leukocyte antigen class II gene diversity tunes antibody repertoires to common pathogens

Allelic diversity of HLA class II genes may help maintain humoral immunity against infectious diseases. We investigated the relative contribution of specific HLA class II alleles, haplotypes and genotypes on the variation of antibody responses to a variety of common pathogens in a cohort of 800 adults representing the general Arab population. We found that classical HLA class II gene heterozygosity confers a selective advantage. Moreover, we demonstrated that multiple HLA class II alleles play a synergistic role in shaping the antibody repertoire. Interestingly, associations of HLA-DRB1 genotypes with specific antigens were identified. Our findings suggest that HLA class II gene polymorphisms confer specific humoral immunity against common pathogens, which may have contributed to the genetic diversity of HLA class II loci during hominine evolution.