HLA-B27: what's new?

Abstract

The HLA-B27 molecule is one of the most fascinating in medicine. Its contribution to the aetiopathogenesis of SpA and other diseases, and its protective action in certain infections, continue to challenge our understanding of its immunobiology and physiological roles. Animal studies have helped to cast light on ways in which HLA-B27 exerts its effects. Subtle variations in structure and behaviour between B27 subtypes that are strongly associated with SpA, compared with those whose association is neutral or weak, are helping to elucidate its pathogenetic mechanisms. However, none of the current hypotheses fully explains the observed actions of HLA-B27. Consequently, attention is turning to how haplotype linkages and genetic networks involving other MHC and non-MHC genes influence the penetrance and clinical expression of B27. HLA-B27 gives an intriguing insight into the connection between heredity and disease. As well as its close links with SpA, various other associations have been reported between B27 and diseases of different organs and systems. Evidence is also accumulating that it mitigates the virulence of HIV and other viral infections. The role of HLA-B27 as an aid to diagnosis, prognosis and disease management is gradually becoming clearer.

A Close Association of Autoimmune-Mediated Processes and Autoimmune Disorders with Chronic Myelomonocytic Leukemia: Observation from a Single Institution

“…For example, HLA B27 has been reported in a few AIDs, such as ankylosing spondylitis, uveitis, psoriasis, amyloidosis and aortitis [48,49]. In addition, a number of polymorphic genes, such as HLA-DRB1, TAP2*0201, TNF2 and PTPN22, affect the susceptibility for acquiring various kinds of AIDs [50], but their roles in MDS or CMML are unknown.…”

Prevalence of diastolic dysfunction in patients with ankylosing spondylitis: a cross-sectional study

“…Ankylosing spondylitis (AS) is a rheumatic disease with a strong genetic association with the human leucocyte antigen (HLA) B27 (4). Extra-articular manifestations are common and include cardiac abnormalities (5), which may be caused by inflammation and loss of elastic tissue (6,7).…”

Molecular mechanism of the susceptibility difference between HLA-B*27:02/04/05 and HLA-B*27:06/09 to ankylosing spondylitis: substitution analysis, MD simulation, QSAR modelling, andin vitroassay

“…HLA-B*27:05 is deemed to be the genetic ancestor from which the other B27 alleles have evolved, and has been found to strongly associate with AS [9]. Here, a total of 218 9-mer antigenic peptides with experimentally measured affinity (pBL 50 ) to the subtype were retrieved from a recent report [22] (see Supporting Information Table S1, available online).…”

“…Epidemiological investigations revealed a strong association between AS and the three HLA-B2 subtypes B*27:02, B*27:04 and B*27:05, whereas there are two subtypes, B*27:06 and B*27:09, that apparently lack an association with AS [8]. AS has also been reported in individuals with some other subtypes, but most are extremely rare and their relationship to the disease has not been defined [9].…”

“…This would allow the response of HLA-B27-restricted cross-reactive cytotoxic T-lymphocytes to a foreign peptide to be directed against self-peptides as well. The autoimmune reaction might then lead to chronic inflammation [9]. Strikingly, the property difference between the peptide-binding grooves of most HLA-B27 subtypes is modest, commonly with only few residue changes.…”