B*2705-β2MG with bound peptide
Alleles	B*2701, 2702, 2703, . . .
Structure (See HLA-B HLA-B HLA-B is a human gene that provides instructions for making a protein that plays a critical role in the immune system. HLA-B is part of a family of genes called the human leukocyte antigen complex... )		Available 3D structures
EBI-HLA European Bioinformatics Institute The European Bioinformatics Institute is a centre for research and services in bioinformatics, and is part of European Molecular Biology Laboratory...	B*2701
	B*2702
	B*2703
	B*2704
	B*2705	, , , , , , , , ,
	B*2706
	B*2709	, , ,

Human Leukocyte Antigen (HLA) B27 (subtypes B*2701-2759) is a class I surface antigen

Antigen

An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...

 encoded by the B locus in the major histocompatibility complex

Major histocompatibility complex

Major histocompatibility complex is a cell surface molecule encoded by a large gene family in all vertebrates. MHC molecules mediate interactions of leukocytes, also called white blood cells , which are immune cells, with other leukocytes or body cells...

 (MHC) on chromosome 6 and presents antigenic peptide

Peptide

Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...

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

T cell

T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...

s. HLA-B27 is strongly associated with ankylosing spondylitis

Ankylosing spondylitis

Ankylosing spondylitis , previously known as Bekhterev's disease, Bekhterev syndrome, and Marie-Strümpell disease is a chronic inflammatory disease of the axial skeleton with variable involvement of peripheral joints and nonarticular structures...

 (AS), and other associated inflammatory diseases referred to collectively as "spondyloarthritis

Spondyloarthropathy

Spondyloarthropathy is any joint disease of the vertebral column. Spondyloarthropathy with inflammation is called spondylarthritis. In contrast, spondylopathy is a disease of the vertebra itself, but many conditions involve both spondylopathy and spondyloarthropathy...

".

The prevalence of HLA-B27 varies markedly in the general population. For example, about 8% of Caucasians

Caucasian race

The term Caucasian race has been used to denote the general physical type of some or all of the populations of Europe, North Africa, the Horn of Africa, Western Asia , Central Asia and South Asia...

, 4% of North Africans, 2-9% of Chinese

Han Chinese

Han Chinese are an ethnic group native to China and are the largest single ethnic group in the world.Han Chinese constitute about 92% of the population of the People's Republic of China , 98% of the population of the Republic of China , 78% of the population of Singapore, and about 20% of the...

, and 0.1-0.5% of persons of Japanese

Yamato people

is a name for the dominant native ethnic group of Japan. It is a term that came to be used around the late 19th century to distinguish the residents of the mainland Japan from other minority ethnic groups who have resided in the peripheral areas of Japan, such as the Ainu, Ryukyuan, Nivkh, Ulta, as...

 descent possess this gene. In northern Scandinavia

Scandinavia

Scandinavia is a cultural, historical and ethno-linguistic region in northern Europe that includes the three kingdoms of Denmark, Norway and Sweden, characterized by their common ethno-cultural heritage and language. Modern Norway and Sweden proper are situated on the Scandinavian Peninsula,...

 (Lapland

Lapland (region)

Lapland is a region in northern Fennoscandia, largely within the Arctic Circle. It streches across Norway, Sweden, Finland and the Kola Peninsula . On the North it is bounded by the Barents Sea, on the West by the Norwegian Sea and on the East by the White Sea...

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

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.

B27 serotype recognition of Some HLA B*27 allele-group gene products

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

HLA B*2702 frequencies

		freq
ref.	Population	(%)
	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
	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
	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

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

Pathology

Pathology is the precise study and diagnosis of disease. The word pathology is from Ancient Greek , pathos, "feeling, suffering"; and , -logia, "the study of". Pathologization, to pathologize, refers to the process of defining a condition or behavior as pathological, e.g. pathological gambling....

, it does not appear to be the sole mediator in development of disease

Disease

A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...

. For example, while 90% of people with ankylosing spondylitis

Ankylosing spondylitis

Ankylosing spondylitis , previously known as Bekhterev's disease, Bekhterev syndrome, and Marie-Strümpell disease is a chronic inflammatory disease of the axial skeleton with variable involvement of peripheral joints and nonarticular structures...

 (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. Additionally there are potential environmental factors (triggers) that may also play a role in susceptible individuals.,

HLA B27 Gene frequencies

	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.

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.

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.

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

Beta-2 microglobulin

β2 microglobulin also known as B2M is a component of MHC class I molecules, which are present on all nucleated cells . In humans, the β2 microglobulin protein is encoded by the B2M gene.-Structure and function:...

 causes the protein to be misfolded, therefore initiating the unfolded protein response

Unfolded protein response

The unfolded protein response is a cellular stress response related to the endoplasmic reticulum. It is a stress response that has been found to be conserved between all mammalian species, as well as yeast and worm organisms...

 (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.

Associated pathology

In addition to its association with ankylosing spondylitis, HLA-B27 is implicated in other types of seronegative spondyloarthropathy as well, such as reactive arthritis

Reactive arthritis

Reactive arthritis , is classified as an autoimmune condition that develops in response to an infection in another part of the body. Coming into contact with bacteria and developing an infection can trigger the disease. Reiter's syndrome has symptoms similar to various other conditions collectively...

 (Reiter's Syndrome), certain eye disorders such as acute anterior uveitis

Uveitis

Uveitis specifically refers to inflammation of the middle layer of the eye, termed the "uvea" but in common usage may refer to any inflammatory process involving the interior of the eye....

 and iritis

Iritis

Iritis is a form of anterior uveitis and refers to the inflammation of the iris of the eye.-Types:There are two main types of iritis: acute and chronic. They differ in numerous ways....

, psoriatic arthritis

Psoriatic arthritis

Psoriatic arthritis is a type of inflammatory arthritis that, according to the National Psoriasis Foundation, will develop in up to 30 percent of people who have the chronic skin condition psoriasis...

 and ulcerative colitis

Ulcerative colitis

Ulcerative colitis is a form of inflammatory bowel disease . Ulcerative colitis is a form of colitis, a disease of the colon , that includes characteristic ulcers, or open sores. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset...

associated spondyloarthritis. The shared association with HLA-B27 leads to increased clustering of these diseases.

External links

by A. Luisa Di Lorenzo, MBBCh

• BASDAI and Ankylosing Spondylitis