An update on the contribution of the MHC to as susceptibility

Abstract

The 40-year-old association of HLA-B27 with ankylosing spondylitis is one of the best examples of disease association with a hereditary marker. Genomewide association and family studies suggest that other important major histocompatibility complex (MHC) influences are operative in ankylosing spondylitis (AS) susceptibility. HLA-B27 positive hepatitis C individuals are immunologically more efficient in combating viral infections such as HIV-1, hepatitis C, and influenza and less efficient in combating against certain bacteria (and perhaps other organisms) capable of surviving intracellularly. A recent representative population survey of the frequency of HLA-B27 in the USA found a lower frequency of HLA-B27 in older US adults, perhaps reflecting this. Other HLA class I and class II alleles have been implicated in AS susceptibility, the most consistent being HLA-B*40/B60 (B*40:01) but also B14, B15, A*0201, DRB1*04:04, and certain DPA1 and DPB1 alleles. Non-HLA MHC alleles have also been implicated, although many such studies have been inconsistent, likely due to power issues related to the low number of HLA-B27-negative AS patients examined. The best evidence is for major histocompatibility complex class I chain-related gene A (MICA) whose recognition by intestinal epithelial T cells expressing different V-delta-1 gamma/delta TCR further implicates the gut in AS pathogenesis. The HLA class I and class II and other non-HLA allelic associations underscore the importance of T cells in AS pathogenesis.

Quantitative Proteomic Analysis of Peripheral Blood Mononuclear Cells in Ankylosing Spondylitis by iTRAQ

“…Ankylosing Spondylitis (AS) is an autoimmune disease, which is characterized by involving the axial joint and ligament and tendon adhesion of inflammatory changes . Since it is subject to genetic and environment factors, the pathogenesis of AS is very complex . Recent studies have demonstrated that NK cells are generally considered to play important roles in the process of cell killing and are associated with the pathogenesis of AS .…”

“…1,2 Since it is subject to genetic and environment factors, the pathogenesis of AS is very complex. 3,4 Recent studies have demonstrated that NK cells are generally considered to play important roles in the process of cell killing and are associated with the pathogenesis of AS. 5,6 Isobaric tags for relative and absolute quantitation (ITRAQ) is widely used for generating quantitative proteomic expression profi les and is regarded as a powerful new tool for proteomic research in many autoimmune diseases.…”

Human HLA‐B27 typing using the BD™ HLA‐B27 kit on the BD FACSVia™ system: A multicenter study

“…One of the eight was confirmed as HLA‐B27 negative by the molecular typing method, resulting in one false positive outcome on the BD FACSVia system. Four “Inconclusive” determinations reported on the BD FACSVia system [and negative or positive on the BD FACSCalibur] were confirmed by the molecular typing method as either HLA‐B27 negative or positive, matching the BD FACSCalibur determinations. None of the HLA‐B27 positive samples determined by the molecular typing method was identified as negative by either system.…”

“…HLA‐B27 is a class I antigen molecule of the major histocompatibility complex. It is well documented that HLA‐B27 is a genotype common to a number of rheumatic inflammatory disorders, such as ankylosing spondylitis (AS), Reiter's syndrome, acute anterior uveitis, as well as inflammatory bowel disease . HLA‐B27 is strongly associated with AS, a systemic inflammatory disease that affects the spine and the sacroiliac and peripheral joints.…”

Reactive arthritis – an interdisciplinary issue

“…HLA-B27 is a highly polymorphic molecule containing over 116 protein subtypes; HLA-B27:01 and B27:117 subtypes are best known. Currently, considering the antigen structure, the most similar to HLA-B27 is HLA-B40, B40:01 subtype to be more precise [6].…”