The cross-tolerance hypothesis, HLA-B27 and ankylosing spondylitis

The association of HLA-B27 with ankylosing spondylitis (AS) can be explained by a cross-tolerance hypothesis, which suggests that Gram-negative bacteria, such as Klebsiella, possess antigens which resemble HLA-B27. Experimental studies with human tissue-typing sera and rabbit anti-Klebsiella sera would appear to be compatible with this hypothesis. Clinical studies indicate that faecal Klebsiella can be isolated more readily from AS patients during active phases of the disease, when this is defined either clinically, with or without uveitis, or biochemically by elevation in ESR and C-reactive protein levels. The cross-tolerance hypothesis proposes that ankylosing spondylitis is a reactive arthritis following infection by Gram-negative bacteria and tissue damage is produced by antibacterial antibody binding to cross-reacting self-antigens.