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HLA-B27

From SNPedia

HLA-B27 Syndromes[edit]

Medscape: HLA-B27 Syndromes
HLA-B*27:05 and HLA-B*27:04 (but not HLA-B*27:09 [PMID 20167541] [PMID 21428748] [PMID 12042320]) are associated with ankylosing spondylitis, sacroiliitis, acute anterior uveitis, reacitve arthritis (formerly Reiter's syndrome). psoriasis, psoriatic arthritis, Crohn's disease, ulcerative colitis and inflammatory bowel disease.

Tag SNPs for HLA-B27[edit]

Commonly tested:[edit]

Also tested[edit]

HLA-B27 subtypes and their worldwide distribution[edit]

A Map of Prehistoric Human Migrations with Locations of HLA-B27 Subtypes Superimposed [PMID 24838411]

HLA-B27 subtypes and predispositions[edit]

HLA-B*27:09 does not predispose for ankylosing spondylitis although it differs from B*27:05, the most common and AS-associated subtype in different ethnic groups, only for the substitution His116Asp.

[PMID 21428748]
HLA B27 is distributed throughout the world with the prevalence of spondyloarthropathy correlating with the frequency of HLA B27 in the population. For example, HLA B27 is rare in Africa and spondyloarthropathy is rare on that continent. HLA B27 is extremely common in the Haida Pacific Northwest Indian tribe and AS is correspondingly common. HLA B27 was initially typed using serological methods. More recent typing methods have appreciated that serology does not distinguish many subsets of HLA B27 that can be defined by DNA sequencing. This molecular typing allows the recognition of more than 60 subtypes of HLA B27.13 The most common subtype is designated HLA B2705. All common subtypes are associated with predisposition to AS with the exceptions of B2706 which is common in Sardinia and B2709

[PMID 24261772] Results:
(1) A total of 38 studies, including 3,410 AS cases and 1,735 healthy controls, were collected in this meta-analysis. (2) Our results showed that B2704 was a risk factor but B2703, B2706, B2707, B2727, B2729, and B2747 may be protective factors for AS worldwide. (3) These subtypes, such as B2701, B2702, B2705, B2708-15, B2717-20, B2723-24, B2733, B2735, B2740, B2746, B2749, and B2767, showed no association with susceptibility to AS. There was a huge difference with previous reports for B2702 and B2705. (4) The B2702, B2704 and B2705 subtypes have existed high heterogeneity but no publication bias.

The Pathophysiology of HLA-B27:[edit]

An update on the contribution of the MHC to AS susceptibility: The role of HLA-B27 [PMID 24838411]

"t has also been shown that HLA-B27-positive individuals have altered intracellular killing in certain infections, suggesting that infection or immune response may act as a trigger of spondyloarthopathies.

In the last few years, we have begun to learn how profoundly the microbiome shapes the immune response. As a gene that codes for a protein that presents antigen to induce an immune response and that also regulates positive and negative selection of T cells in the thymus, HLA-B27 almost certainly does have an effect on normal human microbial flora. It is possible that additional properties of HLA-B27, such as dimerization, its effect on the unfolded protein response, or its high sequence identity with bacterially derived proteins, all affect bacterial colonization. However, the vast diversity of gut flora and the rather primitive understanding of this diversity make it difficult to quantify how HLA-B27 alters this flora."

[http://www.jrheum.org/content/35/3/480.full.pdf A Comparison of Self-reported Joint Symptoms Following Infection with Different Enteric Pathogens: Effect of HLA-B27] [PMID 18203313]
Results. Of 3146 patients invited, 2105 (67%) responded to the survey questionnaire. The triggering infections were Campylobacter, 1003; Salmonella, 619; E. coli, 290; Shigella, 102; and Yersinia, 91. Reactive joint pain was reported by 294 subjects: Campylobacter, 131 (13.1%); Salmonella, 104 (16.8%); Yersinia, 21 (23.1%); Shigella, 10 (9.8%); and E. coli, 28 (9.7%). There was a significant association between severity of gastroenteritis and development of arthralgia (p = 0.001).

Possible link to Klebsiella intestinal bacteria and diet:[edit]

The link between Klebsiella and ankylosing spondylitis in worldwide geographical locations. [PMID 27030252]

The link between ankylosing spondylitis, Crohn's disease, Klebsiella, and starch consumption. [PMID 23781254] "Both ankylosing spondylitis (AS) and Crohn's disease (CD) are chronic and potentially disabling interrelated conditions, which have been included under the group of spondyloarthropathies. The results of a large number of studies support the idea that an enteropathic pathogen, Klebsiella pneumoniae, is the most likely triggering factor involved in the initiation and development of these diseases. Increased starch consumptions by genetically susceptible individuals such as those possessing HLA-B27 allelotypes could trigger the disease in both AS and CD by enhancing the growth and perpetuation of the Klebsiella microbes in the bowel. Exposure to increased levels of these microbes will lead to the production of elevated levels of anti-Klebsiella antibodies as well as autoantibodies against cross-reactive self-antigens with resultant pathological lesions in the bowel and joints. Hence, a decrease of starch-containing products in the daily dietary intake could have a beneficial therapeutic effect on the disease especially when used in conjunction with the currently available medical therapies in the treatment of patients with ankylosing spondylitis and Crohn's disease."

Raised incidence of ankylosing spondylitis among Inuit populations could be due to high HLA-B27 association and starch consumption. [PMID 25385438]

"Ankylosing spondylitis (AS) is a chronic inflammatory arthritis mainly affecting the spinal joints. It would appear that the most likely causative agent in the development of AS is an environmental factor in the genetically susceptible, HLA-B27 positive, individuals. Extensive data from several countries support the notion that Klebsiella pneumonia bacteria are the most likely culprit in the causation of AS. These microbes possess antigens which resemble HLA-B27 and spinal collagens. Increased intake of high-starch diet is directly proportional to the gut-associated bacterial load, especially in the large intestine, and among these microbial agents, Klebsiella is considered as one of the main constituting components. Therefore, a low-starch diet intake alongside the currently used medical therapeutic modalities could be beneficial in the management of patients with early AS. It is suggested that a change in the dietary habits from high protein, low-starch marine components to the Westernized high-starch diet among the Inuit peoples of Alaska and Canada could be considered as one of the main contributing factors in the increased prevalence of AS during the last few decades within this genetically unmixed native population."

Possible link to Chlamydia infection[edit]

Novel HLA-B27-restricted epitopes from Chlamydia trachomatis generated upon endogenous processing of bacterial proteins suggest a role of molecular mimicry in reactive arthritis. [PMID 23867464]

HLA-B27 Associated Diseases[edit]

Acute Anterior Uveitis[edit]

Of patients with acute anterior uveitis, 50-60% may be HLA-B27 positive.
Studies indicate that HLA-B27 associated uveitis is a distinct entity characterized by a male predominance and frequent association with seronegative arthritic syndromes, such as ankylosing spondylitis, reactive arthritis, psoriatic arthritis, and inflammatory bowel disease. The first episode of HLA-B27 associated acute anterior uveitis most commonly occurs in patients aged 20-40 years, whereas the age of onset of HLA-B27-negative acute anterior uveitis tends to occur a decade later. Of patients with acute anterior uveitis, 50-60% may be HLA-B27 positive. It is generally a benign nongranulomatous unilateral disease presenting as a classic triad of pain, redness, and photophobia.

HLA-B27 associated acute anterior uveitis is the most frequent type of endogenous uveitis, accounting for 18-32% of all anterior uveitis cases in western countries and for 6-13% of all anterior uveitis cases in Asia. The relatively lower frequency in Asia is related to the lower frequency of HLA-B*27:05 and HLA-B*27:02 and the higher frequency of HLA-B*27:09 found in this population.

Ankylosing Spondylitis[edit]

Ankylosing spondylitis may first present to an ophthalmologist in the form of acute anterior uveitis. A family history or symptoms of back problems and a positive HLA-B27 are highly suggestive of the diagnosis.

HLA-B27 is found in 88% of patients with ankylosing spondylitis. It is inherited in a Mendelian fashion, and it is found in 50% of first-degree relatives of those patients with spondyloarthropathies who are HLA-B27 positive. The chance that an HLA-B27 patient will develop spondyloarthritis or eye disease is 1 in 4.

Reactive Arthritis[edit]

Reactive arthritis occurs like ankylosing spondylitis in individuals who are HLA-B27 positive; in fact, 60-85% of patients are HLA-B27 positive.
The disease is most common in persons aged 18-40 years, but it has been known to occur in children and older adults. The sex ratio varies, depending on whether the infection is enteric or venereally acquired. The sex ratio following gastrointestinal infection is 1:1, whereas the genitourinary disease primarily affects males. Prevalence of the disease also is high in homosexual and bisexual men, owing to the high rate of genitourinary and gastrointestinal infections in this group. A particular severe form of peripheral spondyloarthropathy following an infection has been described in patients with AIDS.

Associations of Reactive Arthritis with bacterial infections[edit]

The first bacterial infection noted to be causally related to reactive arthritis was Shigella flexneri. Other bacteria that have been implicated in reactive arthritis include several Salmonella species, Yersinia enterocolitica, Campylobacter jejuni, Chlamydia trachomatis, Chlamydia pneumoniae, Clostridium difficile, and Ureaplasma.

Inflammatory Bowel Disease: Ulcerative Colitis and Crohn's Disease[edit]

Ulcerative colitis and Crohn's disease are associated with acute anterior uveitis. Specifically, 2.4% of patients with Crohn disease and 5-12% of patients with ulcerative colitis develop acute anterior uveitis. Sometimes, the iritis predates the bowel disease, which may sometimes be asymptomatic. Approximately 50-75% of patients with spondylitis in association with inflammatory bowel disease have HLA-B27. In contrast, patients who develop sclerouveitis in the presence of inflammatory bowel disease tend to be HLA-B27 negative, and these patients do not develop sacroiliitis.

Psoriasis and Psoratic Arthritis[edit]

The prevalence of arthritis in patients with psoriasis is higher than that found in the general population. It occurs in about 5-42% of patients with psoriasis. HLA-B27 is associated with the pustular form of psoriasis, and the association of HLA-B27 in peripheral psoriatic arthritis is weak. In the presence of spondylitis associated with psoriasis, 60-70% of these cases are HLA-B27 positive.

External links[edit]