The Human Leukocyte Antigen HLA-B27 is strongly associated with development of a group of inflammatory arthritides including Ankylosing Spondylitis and Reactive Arthritis (ReA). The link between HLA-B27 and Ankylosing Spondylitis was first discovered independently by groups in Britain and the USA in 1973 [1–3].
We still do not know for sure why B27 causes AS, but we do know that the natural function of HLA-B27 is to bind and present intracellular antigenic peptides for cell surface presentation to Cytotoxic T lymphocytes (CTL). HLA-B27 may cause AS by presenting “arthritogenic” peptides to pathogenic T cells. Alternatively HLA-B27 may cause AS because it has an abnormal cell biology. Thus B27 can form homodimers (B272) both intracellularly and on the cell surface . Cell surface B272 may have a pathogenic role in AS by binding Natural Killer family receptors, including KIRs (killer Ig-like receptors) and/or LILRs (leukocyte Ig-like receptors). KIRs are expressed on both Natural Killer Cells and T cells, whilst LILRs are found on monocytes, B lymphocytes and dendritic cells. We have shown that, in SpA, an increased number of peripheral blood NK and CD4 T cells express the KIR3DL2 receptor compared to healthy controls and RA patients. These cells are enriched for IL17 production. Recent GWAS studies have implicated the Th17 pathway (and confirmed the role of HLA-B27). The mysterious and ever changing role of B27 from 1973 to 2014 will be discussed in this presentation.
Caffrey M & James DCO Human Lymphocyte Antigen Association in Ankylosing Spondylitis Nature 242, 121 (09 March 1973).
Schlosstein L, Terasaki PI, Bluestone R, Pearson CM. High association of an HL-A antigen, W27, with ankylosing spondylitis. N Engl J Med. 1973 Apr 5;288(14):704-6.
Brewerton DA, Hart FD, Nicholls A, Caffrey M, James DC, Sturrock RD. Ankylosing spondylitis and HL-A 27. Lancet. 1973 Apr 28;1(7809):904-7.
Allen, RL, O' Callaghan C, McMichael AJ and Bowness P. Cutting edge: HLA B27 can form a novel beta 2-microglobulin-free heavy chain homodimer structure J. Immunol. 1999. 162, 5045-5048.
Disclosure of Interest None declared
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