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 The major histocompatibility complex (MHC) is a large Locus (genetics), locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for Cell (biology), cell surface proteins essential for the adaptive immune system. The ...

(MHC) on

chromosome 6 Chromosome 6 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 6 spans nearly 171 million base pairs (the building material of DNA) and represents between 5.5 and 6% of the total DNA i ...

and presents antigenic

peptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty am ...

s (derived from self and non-self antigens) to

T cell T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell ...

s. HLA-B27 is strongly associated with

ankylosing spondylitis Ankylosing spondylitis (AS) is a type of arthritis from the disease spectrum of axial spondyloarthritis. It is characterized by long-term inflammation of the joints of the spine, typically where the spine joins the pelvis. With AS, eye and bow ...

and other associated inflammatory diseases, such as

psoriatic arthritis Psoriatic arthritis (PsA) is a long-term inflammatory arthritis that may occur in some people affected by the autoimmune disease psoriasis. The classic features of psoriatic arthritis include dactylitis (sausage-like swelling of the fingers ...

inflammatory bowel disease Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine, with Crohn's disease and ulcerative colitis (UC) being the principal types. Crohn's disease affects the small intestine and large intestine ...

, and

reactive arthritis Reactive arthritis, previously known as Reiter's syndrome, is a form of inflammatory arthritis that develops in response to an infection in another part of the body (cross-reactivity). Coming into contact with bacteria and developing an infect ...

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 North Africa (sometimes Northern Africa) is a region encompassing the northern portion of the African continent. There is no singularly accepted scope for the region. However, it is sometimes defined as stretching from the Atlantic shores of t ...

, 2–9% of

Chinese Chinese may refer to: * Something related to China * Chinese people, people identified with China, through nationality, citizenship, and/or ethnicity **Han Chinese, East Asian ethnic group native to China. **'' Zhonghua minzu'', the supra-ethnic ...

, and 0.1–0.5% of persons of

Japanese Japanese may refer to: * Something from or related to Japan, an island country in East Asia * Japanese language, spoken mainly in Japan * Japanese people, the ethnic group that identifies with Japan through ancestry or culture ** Japanese diaspor ...

descent possess the gene that codes for this antigen. Among the

Sami Acronyms * SAMI, ''Synchronized Accessible Media Interchange'', a closed-captioning format developed by Microsoft * Saudi Arabian Military Industries, a government-owned defence company * South African Malaria Initiative, a virtual expertise ne ...

in Northern

Scandinavia Scandinavia is a subregion#Europe, subregion of northern Europe, with strong historical, cultural, and linguistic ties between its constituent peoples. ''Scandinavia'' most commonly refers to Denmark, Norway, and Sweden. It can sometimes also ...

(

Sápmi is the cultural region traditionally inhabited by the Sámi people. Sápmi includes the northern parts of Fennoscandia, stretching over four countries: Norway, Sweden, Finland, and Russia. Most of Sápmi lies north of the Arctic Circle, boun ...

), 24% of people are HLA-B27 positive, while 1.8% have associated ankylosing spondylitis, 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

and approximately 70–80% of patients with

have the genetic marker.

Disease associations

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

diseases A disease is a particular abnormal condition that adversely affects the structure or function of all or part of an organism and is not immediately due to any external injury. Diseases are often known to be medical conditions that are asso ...

has not yet been fully elucidated. Though HLA-B27 is associated with a wide range of

pathology Pathology is the study of disease. The word ''pathology'' also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when used in the context of modern medical treatme ...

, it does not appear to be the sole mediator in the development of disease. 90% of people with

(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. 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

have the HLA-B27

genotype The genotype of an organism is its complete set of genetic material. Genotype can also be used to refer to the alleles or variants an individual carries in a particular gene or genetic location. The number of alleles an individual can have in a ...

. HLA-B27 is implicated in other types of seronegative spondyloarthropathy, such as

, acute anterior

uveitis Uveitis () is inflammation of the uvea, the pigmented layer of the eye between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and ...

iritis Uveitis () is inflammation of the uvea, the pigmented layer of the eye between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and i ...

Crohn's Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea, fever, abdominal distension, and weight loss. Complications outside of the ...

and

ulcerative colitis Ulcerative colitis (UC) is one of the two types of inflammatory bowel disease (IBD), with the other type being Crohn's disease. It is a long-term condition that results in inflammation and ulcers of the colon and rectum. The primary sympto ...

associated spondyloarthritis. The shared association with HLA-B27 leads to increased clustering of these diseases. HLA antigens have been studied in relation to

autism Autism, also known as autism spectrum disorder (ASD), is a neurodevelopmental disorder characterized by differences or difficulties in social communication and interaction, a preference for predictability and routine, sensory processing d ...

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.

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

β2 microglobulin β2 microglobulin (B2M) is a component of MHC class I molecules. MHC class I molecules have α1, α2, and α3 proteins which are present on all nucleated cells (excluding red blood cells). In humans, the β2 microglobulin protein is encoded by t ...

causes the protein to be misfolded, initiating the

unfolded protein response The unfolded protein response (UPR) is a cellular stress response related to the endoplasmic reticulum (ER) stress. It has been found to be conserved between mammalian species, as well as yeast and worm organisms. The UPR is activated in response t ...

(UPR), a pro-inflammatory

endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...

(ER) stress response. Although this mechanism has been demonstrated ''in vitro'' and in animals, there is little evidence of its occurrence in human spondyloarthritis. The ''HLA-B27 heavy chain homodimer formation hypothesis'' suggests that B27 heavy chains tend to dimerise and accumulate in the ER, initiating the UPR. 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

-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. 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

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 nonprogressor Long-term nonprogressors (LTNPs), are individuals infected with HIV, who maintain a CD4 count greater than 500 without antiretroviral therapy with a detectable viral load. Many of these patients have been HIV positive for 30 years without progr ...

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

References

External links

* by A. Luisa Di Lorenzo, MBBCh * * *
BASDAI and Ankylosing Spondylitis
*
National Library of Medicine - Papers on HLA B-27
{{Authority control Immune system disorders 2 Medical mnemonics