HLA-B27
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| B*2705-β2MG with bound peptide 2bst | ||
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major histocompatibility complex (human), class I, B27
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| Alleles | B*2701, 2702, 2703, . . . |
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| Structure (See HLA-B) | Available 3D structures |
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| EBI-HLA | B*2701 | |
| B*2702 | ||
| B*2703 | ||
| B*2704 | ||
| B*2705 | 2bsr, 2bss, 2bst, 2a83, 1w0v, 1uxs, 1ogt, 1hsa, 1jgd, 1jge |
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| B*2706 | ||
| B*2709 | 1w0w, 1uxw, 1of2, 1k5n |
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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 collectively as "spondyloarthritis".
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.[2] In northern Scandinavia (Lapland), 24% of people are HLA-B27 positive, while 1.8% have associated ankylosing spondylitis.
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[edit] Serotype
Note: Serotyping is currently obsolete, as gene sequencing and protein structure determinations are currently used to detect various alleles and subtypes of HLA-B27. Deletion of this chart is suggested. Additionally, the new allele frequency database is obsolete as well.
| B*27 | B27 | Sample | |
| allele | % | % | size (N) |
| 2701 | 100 | 9 | |
| 2702 | 67 | 417 | |
| 2703 | 88 | 26 | |
| 2704 | 97 | 34 | |
| 2705 | 97 | 1197 | |
| 2706 | 97 | 29 |
| freq | ||
| ref. | Population | (%) |
| [4] | Bulgaria | 4.6 |
| Bulgaria Gipsy | 4.5 | |
| Brazil Belo Horizonte | 2.6 | |
| Romanian | 2.2 | |
| Czech Republic | 1.9 | |
| Croatia | 1.7 | |
| Finland | 1.7 | |
| Spain E. Andalusia Gipsy | 1.5 | |
| Tunisia Tunis | 1.1 | |
| [4] | HLA B*2703 frequencies | |
| Romanian | 3.2 | |
| Kenya Nandi | 2.5 | |
| CAR Mbenzele Pygmy | 2.0 | |
| Sudanese | 1.8 | |
| Alaska Yupik Natives | 1.8 | |
| Senegal Niokholo Mandenka | 1.6 | |
| Guinea Bissau | 1.5 | |
| Kenya | 1.4 | |
| Georgia Svaneti Svans | 1.3 | |
| India North Delhi | 1.1 | |
| Ivory Coast Akan Adiopodoume | 1.1 | |
| [4] | HLA B*2704 frequencies | |
| PNG Karimui Plateau | 22.5 | |
| Taiwan Pazeh | 10.9 | |
| PNG West Schrader Ranges | 9.1 | |
| Tibet (China) Tibetans | 7.0 | |
| Taiwan Siraya | 6.9 | |
| Bulgaria Gipsy | 4.5 | |
| New Caledonia | 3.9 | |
| China Guangzhou | 2.5 | |
| India Mumbai Marathas | 2.5 | |
| Singapore Thai | 2.5 | |
| Thailand | 2.0 | |
| China Inner Mongolia | 1.5 | |
| China South Han | 1.2 | |
| Philippines Ivatan | 1.0 | |
| Taiwan Ami | 1.0 |
[edit] Disease associations
[edit] Spondylarthropathies
The relationship between HLA-B27 and many diseases has not yet been fully elucidated. Though it is associated with a wide range of pathology, 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. This raises two important questions: why don't all HLA-B27 positive people develop AS, and why do some people who are HLA-B27 negative develop it? There are additional genes being discovered that also predispose to AS and associated diseases.[5] Additionally there are potential environmental factors (triggers) that may also play a role in susceptible individuals.,[6][7]
| USA Alaska Yupik | 11.5 | |
| Native American | 8.6 | |
| Arizona Pima ind. | 7.9 | |
| Belgium | 7.1 | |
| Mexico Tarahumara | 6.8 | |
| Finland | 6.1 | |
| Ireland South | 4.2 | |
| India Tamil Nadu Nadar | 4.1 | |
| India North Hindus | 3.8 | |
| Croatia | 3.7 | |
| Portugal North | 3.3 | |
| Mexico Guadalajara Mestizos | 2.9 | |
| Czech Republic | 2.8 | |
| Azores Terceira Island | 2.7 | |
| Azores Santa Maria & Sao Miguel | 2.6 | |
| South Korea pop 3 | 2.5 | |
| Cape Verde Northwestern Islands | 2.4 | |
| France South East | 2.3 | |
| Morocco Nador Metalsa Class I | 2.1 | |
| Portugal South | 2.0 | |
| Spain Eastern Andalusia Gipsy | 2.0 | |
| Italy North Pavia | 1.9 | |
| Azores Central Islands | 1.8 | |
| Bulgaria | 1.8 | |
| Israel Jews | 1.8 | |
| Georgia Tibilisi Kurds | 1.7 | |
| Brazil Belo Horizonte | 1.6 | |
| Cape Verde Southeastern Islands | 1.6 | |
| India New Delhi | 1.5 | |
| Mexico Sonora Seri | 1.5 |
Note: These are gene frequencies which are roughly half of the phenotype frequencies.
[edit] 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[8].
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[8].
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 assosiation with β2 microglobulin causes the protein to be misfolded, therefore initiating the unfolded protein response (UPR) - a pro-inflammatory 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[8]. 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.
[edit] Associated pathology
In addition to its association with ankylosing spondylitis, HLA-B27 is implicated in other types of seronegative spondyloarthropathy[9] 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.[10]
[edit] See also
[edit] External links
- HLA-B27 Syndromes at eMedicine by A. Luisa Di Lorenzo, MBBCh
- Bowness P (2002). "HLA B27 in health and disease: a double-edged sword?". Rheumatology (Oxford) 41 (8): 857–68. doi:10.1093/rheumatology/41.8.857. PMID 12154202.
- Online 'Mendelian Inheritance in Man' (OMIM) 142830
- MeSH HLA-B27
- BASDAI and Ankylosing Spondylitis
[edit] References
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Constructs such as ibid., loc. cit. and idem are discouraged by Wikipedia's style guide for footnotes, as they are easily broken. Please improve this article by replacing them with named references (quick guide), or an abbreviated title. (October 2010) |
- ^ 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
- ^ IBID, reference 1
- ^ derived from IMGT/HLA
- ^ a b c d Middleton D, Menchaca L, Rood H, Komerofsky R (2003). "New allele frequency database: http://www.allelefrequencies.net". Tissue Antigens 61 (5): 403–7. doi:10.1034/j.1399-0039.2003.00062.x. PMID 12753660.
- ^ Thomas GP, Brown MA. Genetics and Genomics of Ankylosing Spondylitis. Immunol Rev. 2010; 233:162-180.
- ^ IBID The HLA Complex in Biology and Medicine, Mehra, NK ed
- ^ IBID, Khan MA. Ankylosing Spondylitis
- ^ 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
- ^ Elizabeth D Agabegi; Agabegi, Steven S. (2008). Step-Up to Medicine (Step-Up Series). Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 0-7817-7153-6.
- ^ Kataria, RK; Brent LH (June 2004). "Spondyloarthropathies". American Family Physician 69 (12): 2853–2860. PMID 15222650. http://www.aafp.org/afp/20040615/2853.html.
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