Human Leukocyte Antigen B27 is a class I surface antigen encoded by the B locus in the major
histocompatibility complex on chromosome 6 and presents antigenic peptides to T cells.
HLA-B27 is strongly associated with ankylosing spondylitis, and other associated inflammatory
diseases referred to as "spondyloarthropathies". 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,
24% of people are HLA-B27 positive, while 1.8% have associated ankylosing spondylitis.
A small group of people infected with HIV are able to remain symptom-free for many years
without medication. These "HIV controllers" appear to be slightly more common among people
who are HLA-B27 positive.
Disease associations 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
are HLA-B27 positive, only a fraction of people with HLA-B27 ever develop AS. There are additional
genes being discovered that also predispose to AS and associated diseases. Additionally
there are potential environmental factors that may also play a role in susceptible individuals.
Pathological mechanism of HLA-B27 Due to its strong association with spondyloarthopathies,
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.
Antigen-dependent theories These theories consider a specific combination
of antigen peptide sequence and the binding groove of HLA-B27. 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. Antigen-independent theories
These theories refer to the unusual biochemical properties that HLA-B27 has. The misfolding
hypothesis suggests that slow folding during HLA-B27's tertiatary structure folding and
association with β2 microglobulin causes the protein to be misfolded, therefore initiating
the unfolded protein response - a pro-inflammatory endoplasmic reticulum 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.
Associated pathology In addition to its association with ankylosing
spondylitis, HLA-B27 is implicated in other types of seronegative spondyloarthropathy
as well, such as reactive arthritis, 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.
See also Human leukocyte antigen
External links HLA-B27 Syndromes at eMedicine by A. Luisa
Di Lorenzo, MBBCh Bowness P. "HLA B27 in health and disease:
a double-edged sword?". Rheumatology 41: 857–68. doi:10.109341.8.857. PMID 12154202.
Online 'Mendelian Inheritance in Man' 142830 HLA-B27 at the US National Library of Medicine
Medical Subject Headings BASDAI and Ankylosing Spondylitis
References