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| colspan="3" | 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 </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>

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| colspan="2" bgcolor="#dddddd" | Structure (See HLA-B) || bgcolor="#f4f4f4" |Available<br>3D structures

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| rowspan=7 bgcolor="#e7dcc3" | EBI-HLA

| bgcolor="#eeeeee" | B*2701

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| bgcolor="#eeeeee" | B*2702

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| bgcolor="#eeeeee" | B*2703

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| bgcolor="#eeeeee" | B*2704

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| bgcolor="#eeeeee" | B*2705

| <small> , ,<br>, ,<br>, ,<br> , ,<br> , </small>

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| bgcolor="#eeeeee" | B*2706

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| bgcolor="#eeeeee" | B*2709

|<small>, ,<br> , </small>

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Human leukocyte antigen (HLA) B27 (subtypes B*2701-2759) is a class I surface molecule 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 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%. 4% of North Africans, 2–9% of Chinese, and 0.1–0.5% of persons of Japanese descent possess the gene that codes for this antigen. compared to 14-16% of Northern Scandinavians in general. 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.

Disease associations

The vast majority of patients with positive HLA-B27 will not develop an associated syndrome. 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.

Approximately 40–50% of individuals with psoriatic arthritis have the HLA-B27 genotype.

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.

HLA antigens have been studied in relation to autism.

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.

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 CD8 T-cell response that cross-reacts with a HLA-B27/self-peptide pair. HLA-B27 can bind peptides at the cell surface. 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. 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 β2 microglobulin have been seen on cell surfaces.

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 nonprogressors. The presence of HLA-B27, as well as HLA-B5701, is significantly common among this group.

See also

  • Human leukocyte antigen

References

  • by A. Luisa Di Lorenzo, MBBCh
  • BASDAI and Ankylosing Spondylitis
  • National Library of Medicine - Papers on HLA B-27