New ankylosing spondylitis immunology study findings reported from National Health Service
December 29th, 2008
2008 DEC 29 -- Researchers detail in 'Novel detection of in vivo HLA-B27 conformations correlates with ankylosing spondylitis association,' new data in ankylosing spondylitis. According to recent research published in the journal Arthritis and Rheumatism, "The class I major histocompatibility complex (MHC) molecule HLA-B27 exhibits a strong association with the autoimmune inflammatory arthritis disorder ankylosing spondylitis (AS) and with other related spondylarthropathies. In the absence of both a defined autoimmune response and a target autoantigen(s), the propensity of HLA-B27 to misfold has been hypothesized to be a major parameter in disease pathogenesis."
"We undertook this study to test the hypothesis that HLA-B27 misfolding is due to exposure of cysteine residues within the heavy chain to the oxidizing environment of the endoplasmic reticulum. A rapid acidification and alkylation modification method was used to examine cysteine residue exposure and accessibility within AS-associated and non-AS-associated HLA-B27 subtypes. This novel approach to probing in vivo class I MHC structure revealed that the HLA-B27 heavy chain adopts conformations not previously described. Furthermore, amino acid residues specific to subtypes HLA-B*2706, B*2709, and B*2704 can have an impact on these novel conformations and on cysteine residue exposure. HLA-B27 can adopt novel conformations, resulting in differential accessibility of cysteine residues, which can explain the propensity to misfold," wrote H. Fussell and colleagues, National Health Service.
The researchers concluded: "Cysteine exposure in the HLA-B27 heavy chain is also affected by residues within the 114 and 116 regions, thereby providing a potential biochemical basis for the association of HLA-B27 subtypes with AS."
Fussell and colleagues published their study in Arthritis and Rheumatism (Novel detection of in vivo HLA-B27 conformations correlates with ankylosing spondylitis association. Arthritis and Rheumatism, 2008;58(11):3419-24).
For additional information, contact H. Fussell, National Health Service Blood and Transplant, Colindale Blood Centre, London, UK.
The publisher's contact information for the journal Arthritis and Rheumatism is: Wiley-Liss, Division John Wiley & Sons Inc., 111 River St., Hoboken, NJ 07030, USA.
This article was prepared by Pain & Central Nervous System Week editors from staff and other reports. Copyright 2008, Pain & Central Nervous System Week via NewsRx.com.