Polymorphism of HLA-B27: 105 Subtypes Currently Known

Abstract

HLA-B27 has a high degree of genetic polymorphism, with 105 known subtypes, named HLA-B*27:01 to HLA-B*27:106, encoded by 132 alleles. The most common subtypes associated with ankylosing spondylitis are HLA-B*27:05 (Caucasians), HLA-B*27:04 (Chinese), and HLA-B*27:02 (Mediterranean populations). For Chinese populations, HLA-B*27:04 is associated with a greater ankylosing spondylitis risk than HLA-B*27:05. Two subtypes, HLA-B27*06 and HLA-B27*09, seem to have no disease association. These differential disease associations of HLA-B27 subtypes, and the recent discovery that ERAP1 is associated with ankylosing spondylitis for patients with HLA-B27, have increased attempts to determine the function of HLA-B27 in disease pathogenesis by studying hemodynamic features of its protein structure, alterations of its peptidome, aberrant peptide handling, and associated molecular events. However, after 40 years we still do not fully know how HLA-B27 predisposes to ankylosing spondylitis and related spondyloarthritis.

Human Leukocyte Antigen (HLA) B27 Allotype-Specific Binding and Candidate Arthritogenic Peptides Revealed through Heuristic Clustering of Data-independent Acquisition Mass Spectrometry (DIA-MS) Data

“…HLA-B27, which belongs to the family of HLA class I molecules, is an extremely polymorphic B-locus with more than 100 allelic variants known to date (2,3). The most frequent allotypes with comprehensively described peptide repertoires are HLA-B*27:02-HLA-B*27:09 (4 -18).…”

The relation between ER stress and HLA-B27 misfolding

“…In addition to HLA-B27, also HLA-B27 subtypes have been shown to have different incidences and relations with disease onset. According to previous data analyzing HLA-B27 polymorphisms and clinical symptoms related with spondyloarthropathies, no relations have been found between AS and HLA-B-27:06 or HLA [62,63]. Cytokines analysis is also a reliable marker inflammatory condition, comparing the cytokine profile of HLA-B27 positive and negative patients and healthy controls were performed by several studies.…”

New aspects of spondyloarthritis pathogenesis. Part I. Genetic factors and role of HLA-B27 molecules

“…wśród rasy kaukaskiej jest nim allel B*27:05, w populacji śródziemnomor-skiej allel B*27:02, a u Chińczyków allel B*27:04. Allel B*27:09 nie jest czynnikiem ryzyka, a allelowi B*27:06 przypisuje się działanie protekcyjne [8,9]. Podtypy czą-steczek HLA-B27 kodowane przez różne allele różnią się stabilnością i swoistością wiązania peptydów antygenowych, co wyjaśnia, dlaczego tylko niektóre allele są powiązane z ZZSK.…”