HLA B27 and the genetics of ankylosing spondylitis.

Abstract

SUMMARY 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 patient 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.The finding by Brewerton et al. (1973) and Schlosstein et al. (1973) of a markedly increased frequency of HLA B27 in patients with ankylosing spondylitis raises important questions concerning the genetics and pathogenesis of this disorder. The aims of the present study were to examine the relationship of B27 to ankylosing spondylitis by studying a series of patients to determine (1) if there was evidence of clinical and genetic heterogeneity in ankylosing spondylitis, (2) if dissociation of ankylosing spondylitis from B27 occurs in families, and (3) the prevalence of ankylosing spondylitis in first-degree relatives of B27 positive probands. Patients and methodsPatients were consecutively included in the series after clinical and radiological assessment resulting in a diagnosis of definite ankylosing spondylitis as judged by the New York criteria (Bennett and Wood, 1968). Patients who were found to have psoriasis or inflammatory bowel disease or patients with spondylitis who had been ascertained through a study of patients with uveitis were excluded. HistocompatiAccepted for publication January 24, 1978 504 bility antigen typing was performed in these patients and in 451 controls who were blood donors or members of staff, using a standard microlymphocytoxicity technique (Terasaki and McClelland, 1964). FAMILY STUDIESThese can be divided into 3 separate studies. The first was selective, in which relatives suspected of having a relevant rheumatic disease from the history given by the proband were examined clinically and radiologically and HLA typed. The second was a clinical, radiological, and HLA typing study of parents of 20 HLA B27 positive probands, where both parents were alive and accesssible...

The familial form of spondylarthropathy: A clinical study of 115 multiplex families

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