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Computer illustrations of HLA-B*2705 with influenza nucleoprotein viral peptide in the binding pocket.
B*2705-β2MG with bound peptide 2bst
major histocompatibility complex (human), class I, B27
Alleles B*2701, 2702, 2703, . . .
Structure (See HLA-B) Available
3D structures
EBI-HLA B*2701
B*2705 2bsr, 2bss,
2bst, 2a83,
1w0v, 1uxs,
1ogt, 1hsa,
1jgd, 1jge
B*2709 1w0w, 1uxw,
1of2, 1k5n

Human Leukocyte Antigen (HLA) B27 (subtypes B*2701-2759) [1] 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".

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.[1] 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.[2]

Disease associations[edit]

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. There are additional genes being discovered that also predispose to AS and associated diseases.[3] Additionally there are potential environmental factors (triggers) that may also play a role in susceptible individuals.[1]

Pathological mechanism of HLA-B27[edit]

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.[4]

Antigen-dependent 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.[4]

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 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.[4] 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[edit]

In addition to its association with ankylosing spondylitis, HLA-B27 is implicated in other types of seronegative spondyloarthropathy[5] 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.[6]

See also[edit]

External links[edit]


  1. ^ a b c The HLA Complex in Biology and Medicine | editor: Mehra, NK | "HLA and Spondyloarthropathies" | chapter author: Khan, M.A. | chapter 16 | pages 259-275 | year published: 2010 | Publisher: Jayppee Brothers Medical Publishers, New Delhi, India | ISBN 978-81-8448-870-8
  2. ^ Deeks, S. G., Walker, B. D. Human Immunodeficiency Virus Controllers: Mechanisms of Durable Virus Control in the Absence of Antiretroviral Therapy. Immunity, 2007, 27: 406-416
  3. ^ Thomas GP, Brown MA. Genetics and Genomics of Ankylosing Spondylitis. Immunol Rev. 2010; 233:162-180.
  4. ^ a b c Hacquard-Bouder, C., Ittah, M., Breban, M. Animal models of HLA-B27 associated diseases:new outcoumes. Joint Bone Spine, 2005, 73: 132-138
  5. ^ Elizabeth D Agabegi; Agabegi, Steven S. (2008). Step-Up to Medicine (Step-Up Series). Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 0-7817-7153-6. 
  6. ^ Kataria, RK; Brent LH (June 2004). "Spondyloarthropathies". American Family Physician 69 (12): 2853–2860. PMID 15222650.