HLA-B27 has been well-known for its strong association with spondyloarthropathy for more than 30 years. Much effort has been put forth to uncover the mysterious linkage of this gene with that disease spectrum. With its unique structural characteristic, this molecule was found to bind to a limited number of peptides with arginine at the p2 position, and be weakly associated with β2-microglobulin, which in turn, causes HLA-B27 to appear as a free heavy chain homodimer on the cell surface. These two characteristics have led researchers to propose two important hypotheses trying to explain the role of this molecule in the pathogenesis of spondyloarthropathy: the arthritogenic peptide theory and the unfolded protein response theory. Other researchers have noticed that the presence of HLA-B27 can modulate the bacteriahost interaction and evoke signal transduction. Genes other than HLA-B27 continued to be the focus of other researchers, although data were not so consistent. Molecular mimicry was proposed as a mechanism for disease pathogenesis not long after the linkage of HLA-B27 with ankylosing spondylitis was found. New evidences seem encouraging. Now there are several endogenous and exogenous peptides sharing a similar molecular structure that are claimed to bind to HLA-B27. Needless to say, in the near future, a tremendous amount of evidence will hasten the day when we finally unravel the mystery of HLA-B27 and disease pathogenesis.
Keywords: HLA-B27, pathogenesis, ankylosing spondylitis, arthritogenic peptide, unfolded protein
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