HLA-B27

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HLA-B27, α chain

Existing structural data: s. UniProt

Properties of human protein
Mass / length primary structure 338 amino acids
Cofactor β2-microglobulin
Identifier
Gene name HLA-B
External IDs

Location of the human leukocyte antigens on chromosome 6 with its gene locations HLA-A, -B, -C, -DR, -DQ and -DP.

HLA-B27 is a variant of the human protein complex Human Leukocyte Antigen-B (HLA-B). HLA-B belongs to the group of MHC class I protein complexes that are found on the surface of almost all cells in the organism and regulate important functions of the immune system . MHC complexes present short stretches of protein ( antigens ) on the cell surface where they can be bound by T lymphocytes . Mutations in the HLA-B - gene are with certain autoimmune diseases ( spondyloarthritides accommodated) in combination.

General

The HLA-B gene is located on chromosome 6p 21.33 and consists of a group of more than 100 very similar alleles , which are designated HLA-B * 2701 to HLA-B * 27106. The incidence of HLA-B27 in the European population is around 8% but can be up to 14% in certain regions such as Finland.

Medical importance

HLA-B27 is very strongly associated with the group of spondyloarthritis and has prognostic significance there. For this reason, the distinction between HLA-B27 positive and negative patients in rheumatology is an important criterion in the differential diagnosis.

In its function for the immune system, HLA-B27 appears to bind certain viral antigens particularly effectively compared to other HLA proteins of class 1 . It could be shown that carriers of HLA-B27 infected with HIV show a clearly delayed onset of AIDS . Components of influenza A viruses are also bound particularly well by HLA-B27. The downside of this property of HLA-B27 could, however, represent this very association with the autoimmune diseases mentioned above.

Associated diseases

Finding HLA-B27 in a healthy person does not mean that they have or will develop any of the following diseases. For example, over 90% of patients with ankylosing spondylitis have this MHC-I characteristic, but the prevalence of this disease in Europe is 0.5 to 1%. In contrast, the detection of this marker in a patient with certain spinal problems makes the diagnosis likely.

The following diseases have so far been associated with HLA-B27:

Since the association of HLA-B27 with ankylosing spondylitis was first discovered in 1973, various hypotheses have been put forward as to the cause of this association with certain autoimmune diseases. These hypotheses range from gene coupling with a disease gene to the binding of autoimmune antigens to malfunctions of HLA-B27 itself and could not yet be conclusively clarified. A direct involvement in the diseases of HLA-B27 is now assumed, since transgenic animals with the HLA-B27 gene show similar symptoms. In the meantime, other genes have also been discovered that are directly related to certain diseases, such as a variant of the interleukin-23 receptor in Bechterew's disease.

Extender levamisole in cocaine

Agranulocytosis , which is often fatal, can occur in people who are carriers of HLA-B27 , which is why the anthelmintic levamisole is not used in human medicine, unlike in veterinary medicine. The most dangerous side effects are the aplastic anemia and vasculitis , and also by the reduction of levamisole to Aminorex that pulmonary hypertension . The addition of levamisole to cocaine is increasingly being observed as an extender, which is currently found in approx. 60% of the samples with an average proportion of 7.7%.

Web links

Individual evidence

  1. ^ Paul Bowness: Hla-b27 . In: Annual Review of Immunology . tape 33 , no. 1 , March 21, 2015, ISSN  0732-0582 , p. 29-48 , doi : 10.1146 / annurev-immunol-032414-112110 ( annualreviews.org [accessed January 24, 2019]).
  2. ↑ MA Khan et al. The pathogenetic role of HLA-B27 and its subtypes. In: autoimmune Rev . 2007; 6: 183-189. PMID 17289555 .
  3. ↑ a b A. McMichael, P. Bowness. HLA-B27: natural function and pathogenic role in spondyloarthritis. In: Arthritis Res . 2002; 4 Suppl 3: S153-158. PMID 12110134 .
  4. ↑ M. Huhtinen, A. Karma. HLA-B27 typing in the categorization of uveitis in a HLA-B27 rich population. In: Br J Ophthalmol . 2000 Apr; 84 (4): 413-416. PMID 10729301
  5. ↑ a b c d P. Bowness: HLA B27 in health and disease: a double-edged sword? In: Rheumatology 2002; 41: pp. 857-868 PMID 12154202 PDF .
  6. ↑ a b J.C. Edwards et al. Jekyll and Hyde: the transformation of HLA-B27. In: Immunol Today . 2000 Jun; 21 (6): 256-260. PMID 10825736 .
  7. ↑ Gerd Herold : Internal Medicine. Cologne 2005.
  8. ^ Rheumatology (Oxford). 2002 Oct; 41 (10): 1183-1189 PMID 12364641 , Rheumatology (Oxford). 2006 Sep; 45 (9): 1129-1132 PMID 16522678
  9. ^ WO Dobbins 3rd: HLA antigens in Whipple's disease . January 30, 1987, PMID 2434104
  10. ↑ M. Marcilla, JA López de Castro: Peptides: the cornerstone of HLA-B27 biology and pathogenetic role in spondyloarthritis. In: Tissue Antigens , 2008 Jun; 71 (6), pp. 495-506. PMID 18489433 .
  11. ^ Bernhard Manger, Klaus L. Schmidt, Renate Häfner: Checklist XXL Rheumatology . Georg Thieme Verlag, June 15, 2005, ISBN 978-3-13-151683-1 , pp. 7–.
  12. ↑ Levamisole - Dangerous Extender in Cocaine. STIZ, Tox Center