HLA B27 and the genetics of ankylosing spondylitis

One hundred and twenty-eight of 145 patients with ankylosing spondylitis (AS) were found to be HLA B27 positive. Five patients had evidence of a sero-negative peripheral arthritis resembling peripheral psoriatic arthritis and 3 of these were B27 negative. One further B27 negative patients had a sister with ankylosing spondylitis and ulcerative colitis and a mother with ulcerative colitis. There was evidence of a somewhat later age of onset of symptoms in B27 negative patients. These findings are interpreted as suggesting some degree of clinical and genetic heterogeneity in ankylosing spondylitis with genes for psoriasis and inflammatory bowel disease being important in some individuals, particularly those who are B27 negative. Twenty-five first-degree relatives with ankylosing spondylitis were all B27 positive. The only instance of disassociation of B27 and spondylitis in a family was where the proband had ulcerative colitis as well as spondylitis. Of 13 B27 positive fathers 3 could be diagnosed as having definite ankylosing spondylitis (23%). These findings are thought to provide evidence against the concept that the gene for ankylosing spondylitis is not B27 but a closely linked gene and favour the occurrence of an environmental event affecting approximately one-fifth of B27 positive males to result in disease.