View source for HLA-B27

{{Short description|Type of antigen}}
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|  colspan="3" | [[File:HLA-B*2705-peptide in complex with influenza nucleoprotein NP383-391.png|thumb|HLA-B*2705-peptide (chain A shown in green cartoon, chain B shown in yellow cartoon) complexed to a fragment of the influenza nucleoprotein NP383-391 (orange, sticks). PDB ID 2BST]] 
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| colspan="3" color="white" | <small>B*2705-β2MG with bound peptide {{PDB2|2bst}}</small>
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| align="center" colspan="3" | <div style="font-size:medium; line-height:120%;">major histocompatibility complex (human), class I, B27</div>
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| bgcolor="#e7dcc3" | Alleles  
| colspan = 2  bgcolor="#eeeeee" | B*2701, 2702, 2703, . . . <br> 
|- align="center"
| colspan="2" bgcolor="#dddddd" | '''Structure''' (See [[HLA-B]]) || bgcolor="#f4f4f4" |Available<br>3D structures
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| rowspan=7 bgcolor="#e7dcc3" | [[European Bioinformatics Institute|EBI-HLA]]
| bgcolor="#eeeeee" | [http://www.ebi.ac.uk/cgi-bin/imgt/hla/get_allele.cgi?B*2701 B*2701] {{Webarchive|url=https://web.archive.org/web/20090220123210/http://www.ebi.ac.uk/cgi-bin/imgt/hla/get_allele.cgi?B*2701 |date=2009-02-20 }}
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| bgcolor="#eeeeee" | [http://www.ebi.ac.uk/cgi-bin/imgt/hla/get_allele.cgi?B*2702 B*2702] {{Webarchive|url=https://web.archive.org/web/20090220121327/http://www.ebi.ac.uk/cgi-bin/imgt/hla/get_allele.cgi?B*2702 |date=2009-02-20 }}
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| bgcolor="#eeeeee" | [http://www.ebi.ac.uk/cgi-bin/imgt/hla/get_allele.cgi?B*2703 B*2703] {{Webarchive|url=https://web.archive.org/web/20090220114817/http://www.ebi.ac.uk/cgi-bin/imgt/hla/get_allele.cgi?B*2703 |date=2009-02-20 }}
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| bgcolor="#eeeeee" | [http://www.ebi.ac.uk/cgi-bin/imgt/hla/get_allele.cgi?B*2704 B*2704] {{Webarchive|url=https://web.archive.org/web/20090220114105/http://www.ebi.ac.uk/cgi-bin/imgt/hla/get_allele.cgi?B*2704 |date=2009-02-20 }}
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| bgcolor="#eeeeee" | [http://www.ebi.ac.uk/cgi-bin/imgt/hla/get_allele.cgi?B*2705 B*2705] {{Webarchive|url=https://web.archive.org/web/20090220120219/http://www.ebi.ac.uk/cgi-bin/imgt/hla/get_allele.cgi?B*2705 |date=2009-02-20 }} 
|  <small> {{PDB2|2bsr}}, {{PDB2|2bss}},<br>{{PDB2|2bst}}, {{PDB2|2a83}},<br>{{PDB2|1w0v}}, {{PDB2|1uxs}},<br> {{PDB2|1ogt}}, {{PDB2|1hsa}},<br> {{PDB2|1jgd}}, {{PDB2|1jge}}</small>
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| bgcolor="#eeeeee" | [http://www.ebi.ac.uk/cgi-bin/imgt/hla/get_allele.cgi?B*2706 B*2706] {{Webarchive|url=https://web.archive.org/web/20090220114828/http://www.ebi.ac.uk/cgi-bin/imgt/hla/get_allele.cgi?B*2706 |date=2009-02-20 }}
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| bgcolor="#eeeeee" | [http://www.ebi.ac.uk/cgi-bin/imgt/hla/get_allele.cgi?B*2709 B*2709] {{Webarchive|url=https://web.archive.org/web/20090220114842/http://www.ebi.ac.uk/cgi-bin/imgt/hla/get_allele.cgi?B*2709 |date=2009-02-20 }} 
|<small>{{PDB2|1w0w}}, {{PDB2|1uxw}},<br> {{PDB2|1of2}}, {{PDB2|1k5n}}</small>
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'''Human leukocyte antigen (HLA) B27''' (subtypes B*2701-2759)<ref name=Khan2010>{{cite book |title=The HLA Complex in Biology and Medicine |editor=Narinder K. Mehra |chapter=HLA and spondyloarthropathies |author=M. A. Khan |pages=259–275 |year=2010 |publisher=Jayppee Brothers Medical Publishers |location=New Delhi, India |isbn=978-81-8448-870-8}}</ref> is a class I surface molecule encoded by the B locus in the [[major histocompatibility complex]] (MHC) on [[chromosome 6]] and presents antigenic [[peptide]]s (derived from self and non-self antigens) to [[T cell]]s. HLA-B27 is strongly associated with [[ankylosing spondylitis]] and other associated inflammatory diseases, such as [[psoriatic arthritis]], [[inflammatory bowel disease]], and [[reactive arthritis]].

==Prevalence==
The prevalence of HLA-B27 varies markedly in the global population.

In the United States, the estimated prevalence is 6-8%.<ref name="auto">{{Cite book|url=https://www.ncbi.nlm.nih.gov/books/NBK551523/|title=StatPearls|first1=Padmini|last1=Parameswaran|first2=Michael|last2=Lucke|date=November 30, 2024|publisher=StatPearls Publishing|via=PubMed|pmid=31855367}}</ref> 4% of [[North African#People|North Africans]], 2–9% of [[Han Chinese|Chinese]], and 0.1–0.5% of persons of [[Yamato people|Japanese]] descent possess the gene that codes for this antigen.<ref name=Khan2010 /> Among the [[Sámi people|Sami]] in Northern [[Scandinavia]] ([[Sápmi]]), 24% of people are HLA-B27 positive, while 1.8% have associated ankylosing spondylitis,<ref>{{Cite journal |last1=Johnsen |first1=K. |last2=Gran |first2=J. T. |last3=Dale |first3=K. |last4=Husby |first4=G. |date=October 1992 |title=The prevalence of ankylosing spondylitis among Norwegian Samis (Lapps) |journal=The Journal of Rheumatology |volume=19 |issue=10 |pages=1591–1594 |issn=0315-162X |pmid=1464873}}</ref> compared to 14-16% of Northern Scandinavians in general.<ref>{{Cite journal |last1=Gran |first1=J. T. |last2=Mellby |first2=A. S. |last3=Husby |first3=G. |date=January 1984 |title=The Prevalence of HLA-B27 in Northern Norway |url=http://www.tandfonline.com/doi/full/10.3109/03009748409100382 |journal=Scandinavian Journal of Rheumatology |language=en |volume=13 |issue=2 |pages=173–176 |doi=10.3109/03009748409100382 |issn=0300-9742|url-access=subscription }}</ref><ref>{{Cite journal |last1=Bjelle |first1=Anders |last2=Cedergren |first2=Bertil |last3=Rantapää Dahlqvist |first3=Solbritt |date=January 1982 |title=HLA B 27 in the Population of Northern Sweden |url=http://www.tandfonline.com/doi/full/10.3109/03009748209098109 |journal=Scandinavian Journal of Rheumatology |language=en |volume=11 |issue=1 |pages=23–26 |doi=10.3109/03009748209098109 |issn=0300-9742|url-access=subscription }}</ref> In Finland, an estimated 14% of the population is positive for HLA-B27, while more than 95% of patients with [[ankylosing spondylitis]] and approximately 70–80% of patients with [[reactive arthritis]] have the genetic marker.<ref name = vshp>{{cite web | url = http://www.vshp.fi/medserv/klkemi/fi/ohjekirja/3075.htm | access-date = 2023-04-13 | date = 2014-07-21 | title = Vaasa, laboratorio-ohjekirja Ly-Kudosantigeeni B27 (Vaasa, laboratory manual Ly-Tissue antigen B27) | language = finnish}}</ref>

==Disease associations==

The vast majority of patients with positive HLA-B27 will not develop an associated syndrome.<ref name="auto"/>

The relationship between HLA-B27 and many [[diseases]] has not yet been fully elucidated. Though HLA-B27 is associated with a wide range of [[pathology]], it does not appear to be the sole mediator in the development of disease. 

90% of people with [[ankylosing spondylitis]] (AS) are HLA-B27 positive, although only a small fraction of people with HLA-B27 will develop AS. People who are HLA-B27 positive are more likely to experience early onset AS than HLA-B27 negative individuals.<ref>{{cite journal |last1=Feldtkeller |first1=Ernst |last2=Khan |first2=Muhammad |last3=van der Heijde |first3=Désirée |last4=van der Linden |first4=Sjef |last5=Braun |first5=Jürgen |title=Age at disease onset and diagnosis delay in HLA-B27 negative vs. positive patients with ankylosing spondylitis |journal=Rheumatology International |date=March 2003 |volume=23 |issue=2 |pages=61–66 |doi=10.1007/s00296-002-0237-4 |pmid=12634937 |s2cid=6020403 }}</ref> Research is uncovering other genes that predispose to AS and associated diseases, and there are potential environmental factors that may play a role in susceptible individuals.<ref name="Khan2010" /><ref>{{cite journal |last1=Thomas |first1=Gethin P. |last2=Brown |first2=Matthew A. |title=Genetics and genomics of ankylosing spondylitis |journal=Immunological Reviews |date=January 2010 |volume=233 |issue=1 |pages=162–180 |doi=10.1111/j.0105-2896.2009.00852.x |pmid=20192999 |s2cid=205223192 }}</ref>

Approximately 40–50% of individuals with [[psoriatic arthritis]] have the HLA-B27 [[genotype]].<ref>{{Cite journal|url=https://www.nejm.org/doi/10.1056/NEJMra1505557|title=Psoriatic Arthritis|first1=Christopher T.|last1=Ritchlin|first2=Robert A.|last2=Colbert|first3=Dafna D.|last3=Gladman|date=March 9, 2017|journal=New England Journal of Medicine|volume=376|issue=10|pages=957–970|via=Taylor and Francis+NEJM|doi=10.1056/NEJMra1505557|url-access=subscription}}</ref>

HLA-B27 is implicated in other types of [[seronegative spondyloarthropathy]], such as [[reactive arthritis]], acute anterior [[uveitis]], [[iritis]], [[Crohn's disease]], and [[ulcerative colitis]] associated spondyloarthritis. The shared association with HLA-B27 leads to increased clustering of these diseases.<ref name=agabegi2nd257>{{cite book |author1=Elizabeth D Agabegi |author2=Agabegi, Steven S. |title=Step-Up to Medicine (Step-Up Series) |publisher=Lippincott Williams & Wilkins |location=Hagerstwon, MD |year=2008 |isbn=978-0-7817-7153-5 |url-access=registration |url=https://archive.org/details/stepuptomedicine0000agab }}</ref><ref>{{cite journal | last=Kataria | first=RK | author2=Brent LH | title=Spondyloarthropathies | journal=American Family Physician | volume=69 | issue=12  | date=June 2004 | pages=2853–2860 | url=http://www.aafp.org/afp/20040615/2853.html | pmid=15222650 | access-date=2009-06-29 | archive-date=2008-07-09 | archive-url=https://web.archive.org/web/20080709025335/http://www.aafp.org/afp/20040615/2853.html | url-status=dead }}</ref> 

HLA antigens have been studied in relation to [[autism]].<ref>{{cite journal | last=Torres | first=Anthony | author2=Jonna Westover | title=HLA Immune Function Genes in Autism | journal=Autism Research and Treatment | volume=2012 | issue=12 | pages=2853–2860 | date=February 2012 | doi=10.1155/2012/959073 | pmid=22928105 | pmc=3420779 | doi-access=free }}</ref>

===Pathological mechanism===

HLA-B27 is the most researched HLA-B allele due to its high relationship with spondyloarthropathies. Although it is not apparent how HLA-B27 promotes disease, theories exist and can be divided between antigen-dependent and antigen-independent categories.<ref name="Hacquard">{{cite journal |last1=Hacquard-Bouder |first1=Cécile |last2=Ittah |first2=Marc |last3=Breban |first3=Maxime |title=Animal models of HLA-B27-associated diseases: new outcomes |journal=Joint Bone Spine |date=March 2006 |volume=73 |issue=2 |pages=132–138 |doi=10.1016/j.jbspin.2005.03.016 |pmid=16377230 }}</ref>

====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 from the other HLA-B alleles). The ''arthritogenic peptide hypothesis'' suggests that HLA-B27 has a unique ability to bind antigens from a microorganism that triggers a [[Cytotoxic T cell|CD8 T-cell]] response that cross-reacts with a HLA-B27/self-peptide pair. HLA-B27 can bind peptides at the cell surface.<ref name=":0">{{cite journal |last1=Bowness |first1=Paul |title=HLA-B27 |journal=Annual Review of Immunology |date=21 March 2015 |volume=33 |issue=1 |pages=29–48 |doi=10.1146/annurev-immunol-032414-112110 |pmid=25861975 |doi-access=free }}</ref> The ''molecular mimicry hypothesis'' is similar, although it suggests that cross-reactivity between some bacterial antigens and self-peptides can break tolerance and lead to autoimmunity.<ref name="Hacquard" />

====Antigen-independent theories====

Antigen-independent theories refer to the biochemical properties of HLA-B27. The ''misfolding hypothesis'' suggests that slow folding during HLA-B27's tertiary structure folding and association with [[Beta-2 microglobulin|β2 microglobulin]] causes the protein to be misfolded, initiating the [[unfolded protein response]] (UPR), a pro-inflammatory [[endoplasmic reticulum]] (ER) stress response. Although this mechanism has been demonstrated ''in vitro'' and in animals, there is little evidence of its occurrence in human spondyloarthritis.<ref name=":0" /> The ''HLA-B27 heavy chain homodimer formation hypothesis'' suggests that B27 heavy chains tend to dimerise and accumulate in the ER, initiating the UPR.<ref name="Hacquard" /> 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.

Another misfolding theory published in 2004 proposes that [[Beta-2 microglobulin|β2 microglobulin]]-free heavy chains of HLA-B27 undergo a facile conformational change in which the C-terminal end of domain two, consisting of a long helix, becomes subject to a helix-coil transition involving residues 169–181 of the heavy chain, owing to the conformational freedom newly experienced by domain three of the heavy chain when there is no longer any bound light chain, and owing to the consequent rotation around the backbone dihedral angles of residues 167/168.<ref>{{cite journal |last1=Luthra-Guptasarma |first1=Manni |last2=Singh |first2=Balvinder |title=HLA-B27 lacking associated β2-microglobulin rearranges to auto-display or cross-display residues 169-181: a novel molecular mechanism for spondyloarthropathies |journal=FEBS Letters |date=24 September 2004 |volume=575 |issue=1–3 |pages=1–8 |doi=10.1016/j.febslet.2004.08.037 |pmid=15388324 |doi-access=free }}</ref> The proposed conformational transition is thought to allow the newly-generated coiled region (incorporating residues 'RRYLENGKETLQR' which have also been found to be naturally bound to HLA-B27 as a 9-mer peptide) to bind to either the peptide-binding cleft of the same polypeptide chain (in an act of self-display) or to the cleft of another polypeptide chain (in an act of cross-display). Cross-display is proposed to lead to the formation of large, soluble, high molecular weight (HMW), degradation-resistant, long-surviving aggregates of the HLA-B27 heavy chain. Together with any homodimers formed either by cross-display or by a disulfide-linked homodimerization mechanism, it is proposed that such HMW aggregates survive on the cell surface without undergoing rapid degradation, and stimulate an immune response. Three previously noted features of HLA-B27, which distinguish it from other heavy chains, underlie the hypothesis: (1) HLA-B27 has been found to be bound to peptides longer than 9-mers, suggesting that the cleft can accommodate a longer polypeptide chain; (2) HLA-B27 has been found to itself contain a sequence that has also been actually discovered to be bound to HLA-B27, as an independent peptide; and (3) HLA-B27 heavy chains lacking [[Beta-2 microglobulin|β2 microglobulin]] have been seen on cell surfaces.{{citation needed|date=July 2019}}

=== HIV long-term nonprogressors ===
About 1 in 500 people infected with HIV can remain symptom-free for many years without medication, a group known as [[long-term nonprogressor]]s.<ref>{{cite web |url=https://www.niaid.nih.gov/volunteer/hivlongterm/Pages/default.aspx |title=HIV+ Long-Term Non-Progressor Study |publisher=[[National Institute of Allergy and Infectious Diseases]] |url-status=dead |archive-url=https://web.archive.org/web/20110719205029/http://www.niaid.nih.gov/volunteer/hivlongterm/pages/default.aspx |date=June 23, 2010 |archive-date=July 19, 2011 |access-date=July 5, 2011 }}</ref> The presence of HLA-B27, as well as [[HLA-B57|HLA-B5701]], is significantly common among this group.<ref name="Deeks">{{cite journal |last1=Deeks |first1=Steven G. |last2=Walker |first2=Bruce D. |title=Human Immunodeficiency Virus Controllers: Mechanisms of Durable Virus Control in the Absence of Antiretroviral Therapy |journal=Immunity |date=September 2007 |volume=27 |issue=3 |pages=406–416 |doi=10.1016/j.immuni.2007.08.010 |pmid=17892849 |doi-access=free }}</ref>

==See also==
*[[Human leukocyte antigen]]

==References==
{{Reflist}}

==External links==
* {{EMedicine|article|1201027|HLA-B27 Syndromes}} by A. Luisa Di Lorenzo, MBBCh
* {{cite journal |last1=Bowness |first1=P. |title=HLA B27 in health and disease: a double-edged sword? |journal=Rheumatology |date=1 August 2002 |volume=41 |issue=8 |pages=857–868 |doi=10.1093/rheumatology/41.8.857 |pmid=12154202 |doi-access=free }}
* {{OMIM|142830}}
* {{MeshName|HLA-B27}}
* [http://www.BASDAI.com BASDAI and Ankylosing Spondylitis]
*  [https://www.ncbi.nlm.nih.gov/pubmed/?term=hla+b27 National Library of Medicine - Papers on HLA B-27]

{{HLA-B serotypes}}
{{Authority control}}

[[Category:Immune system disorders]]
[[Category:HLA-B alleles|2]]
[[Category:Medical mnemonics]]