|B*2705-β2MG with bound peptide|
major histocompatibility complex (human), class I, B27
|Alleles||B*2701, 2702, 2703, . . .
|Structure (See HLA-B)||Available
Human leukocyte antigen (HLA) B27 (subtypes B*2701-2759)  is a class I surface antigen encoded by the B locus in the major histocompatibility complex (MHC) on chromosome 6 and presents antigenic peptides (derived from self and non-self antigens) to T cells. HLA-B27 is strongly associated with ankylosing spondylitis (AS), and other associated inflammatory diseases referred to as "spondyloarthropathies". Diseases associated with the HLA-B27 subtype can be remembered with the mnemonic PAIR, and include Psoriasis, Ankylosing spondylitis, Inflammatory bowel disease, and Reiter syndrome.
The prevalence of HLA-B27 varies markedly in the general population. For example, about 8% of Caucasians, 4% of North Africans, 2-9% of Chinese, and 0.1-0.5% of persons of Japanese descent possess this gene. In northern Scandinavia (Lapland), 24% of people are HLA-B27 positive, while 1.8% have associated ankylosing spondylitis.
A small group (<0.5%) of people infected with HIV are able to remain symptom-free for many years without medication. These "HIV controllers" appear to be slightly[vague] more common among people who are HLA-B27 positive.
The relationship between HLA-B27 and many diseases has not yet been fully elucidated. Though it is associated with a wide range of pathology, particularly seronegative spondyloarthropathy, it does not appear to be the sole mediator in development of disease. For example, while 90% of people with ankylosing spondylitis (AS) are HLA-B27 positive, only a fraction of people with HLA-B27 ever develop AS. People who are HLA-B27 positive are more likely to experience early onset AS than HLA-B27 negative individuals. There are additional genes being discovered that also predispose to AS and associated diseases. Additionally there are potential environmental factors (triggers) that may also play a role in susceptible individuals.
Due to its strong association with spondyloarthropathies, HLA-B27 is the most studied HLA-B allele. It is not entirely clear how HLA-B27 influences disease, however there are some prevailing theories as to the mechanism. The theories can be split into antigen-dependent and independent theories.
These theories consider a specific combination of antigen peptide sequence and the binding groove (B pocket) of HLA-B27 (which will have different properties to the other HLA-B alleles). The arthritogenic peptide hypothesis suggests that HLA-B27 has a unique ability to present peptide specific to joints, to autoreactive cytotoxic T cells. The molecular mimicry hypothesis is similar, however it suggests that cross reactivity between some bacterial antigens and self peptide can break tolerance and lead to autoimmunity.
These theories refer to the unusual biochemical properties that HLA-B27 has. The misfolding hypothesis suggests that slow folding during HLA-B27's tertiary structure folding and association with β2 microglobulin causes the protein to be misfolded, therefore initiating the unfolded protein response (UPR) - a pro-inflammatory endoplasmic reticulum (ER) stress response. Also, the HLA-B27 heavy chain homodimer formation hypothesis suggests that B27 heavy chains tend to dimerise and accumulate in the ER, once again, initiating the UPR. Alternatively, cell surface B27 heavy chains and dimers can bind to regulatory immune receptors such as members of the killer cell immunoglobulin-like receptor family promoting the survival and differentiation of pro inflammatory leukocytes in disease.
In addition to its association with ankylosing spondylitis, HLA-B27 is implicated in other types of seronegative spondyloarthropathy as well, such as reactive arthritis (Reiter's Syndrome), certain eye disorders such as acute anterior uveitis and iritis, psoriatic arthritis and ulcerative colitis associated spondyloarthritis. The shared association with HLA-B27 leads to increased clustering of these diseases.
- HLA-B27 Syndromes at eMedicine by A. Luisa Di Lorenzo, MBBCh
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- Online 'Mendelian Inheritance in Man' (OMIM) 142830
- HLA-B27 at the US National Library of Medicine Medical Subject Headings (MeSH)
- BASDAI and Ankylosing Spondylitis
- M. A. Khan (2010). "HLA and spondyloarthropathies". In Narinder K. Mehra. The HLA Complex in Biology and Medicine. New Delhi, India: Jayppee Brothers Medical Publishers. pp. 259–275. ISBN 978-81-8448-870-8.
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