Association of HLA-B*41:02 with Henoch-Schönlein Purpura (IgA Vasculitis) in Spanish individuals irrespective of the HLA-DRB1 status

Abstract

IntroductionA study was conducted to determine whether the human leukocyte antigen (HLA) B alleles are implicated in the susceptibility to Henoch-Schönlein purpura (HSP) in the largest series of Caucasian HSP patients ever assessed for genetic studies.MethodsThe study population was composed of 349 Spanish patients diagnosed with HSP fulfilling the American College of Rheumatology and the Michel et al. classification criteria, and 335 sex and ethnically matched controls. HLA-B phenotypes were determined by sequencing-based typing (SBT) and analyzed by chi-square or Fisher exact test.ResultsA statistically significant increase of HLA-B*41:02 allele in HSP patients when compared with controls was found (8.3% versus 1.5% respectively; P = 0.0001; OR (odds ratio) =5.76 [2.15-19.3]). These results remained statistically significant after adjusting for Bonferroni correction (P = 0.0028). An internal validation also confirmed the susceptibility effect on HSP associated with HLA-B*41:02 (OR = 5.70 [1.98-16.44]). Since a former study described an association between HLA-DRB1*01:03 and HSP susceptibility, we also evaluated the implication of HLA-B*41:02 independently of HLA-DRB1*01:03. Interestingly, the association remained statistically significant (P = 0.0004, OR = 4.97 [1.8-16.9]). No HLA-B association with specific HSP clinical features was found.ConclusionsOur study indicates that HLA-B*41:02 is associated with the susceptibility to HSP in Spanish patients irrespective of HLA-DRB1 status.

A genome-wide association study suggests the HLA Class II region as the major susceptibility locus for IgA vasculitis

“…However, the genetic component of this type of vasculitis remains poorly understood, as only a few candidate gene studies have been performed to date 4, 5 .…”

Variation in the Human Leukocyte Antigen system and risk for endemic Burkitt lymphoma in northern Uganda

“…We suggest that they may point to a role of autoimmunity and/or allergy in eBL. HLA‐B*41 has been linked with Henoch–Schönlein purpura among Spaniards (Lopez‐Mejias et al , ); HLA‐B*58 has been linked with severe cutaneous adverse reactions during treatment with allopurinol, particularly in Asians (Hung et al , ); HLA‐DPB1 variants (homozygosity found in 50% of our controls) have been associated with myasthenia gravis (Horiki et al , ), granulomatosis with polyangiitis, immune reactions to beryllium (Potolicchio et al , ), and antigenic response after transplantation (Shaw et al , ). A role of autoimmunity and/or allergy in BL was suggested by findings that the odds of sporadic BL under age 50 years were decreased in those with a history of allergy or asthma in the International Lymphoma consortium (Mbulaiteye et al , ).…”

A Case of Adult-onset Henoch-Schönlein Purpura Triggered by Fire Ants

“…These HLA types are believed to influence the immunomodulatory functions of IgA and interleukin 1β. Therefore, HLA molecules can increase one's susceptibility to developing HSP or play a protective role and decrease the likelihood of disease onset [12].…”