ROLE OF HEAT-SHOCK PROTEINS IN THE PATHOGENESIS OF CYSTIC-FIBROSIS ARTHRITIS

Background - Arthritis is a well recognised complication of cystic fib rosis. The cause of this arthritis is not yet clear but it is likely t o be an immunological reaction to one of the many bacterial antigens t o which the lungs are exposed. One such group, the heat shock proteins (hsp), was investigated. These are immunodominant antigens of a wide variety of infectious microorganisms and have varying amino acid chain sequences, some of which are similar to those found in human tissues. Methods - Antibodies to human hsp 27 and hsp 90 in the serum of patie nts with cystic fibrosis, with and without arthritis, and in normal ag e and sex matched healthy controls were measured. The severity of the cystic fibrosis was assessed by lung function tests and chest radiogra phs. The nature of the organisms colonising the lungs was determined b y bacteriological examination of sputum. Results - Higher mean titres of serum IgG anti-human hsp 27 and hsp 90 antibodies were found in 50 patients with cystic fibrosis than in healthy controls (hsp 27, 0.25 ( 95% CI 0.19 to 0.33) versus 0.05 (95% CI 0.04 to 0.07); hsp 90, 0.27 ( 95% CI 0.22 to 0.32) versus 0.11 (95% CI 0.08 to 0.14)). These antibod ies were higher in patients in whom the lungs were colonised with Pseu domonas aeruginosa than in those without infection (hsp 27, 0.41 (95% CI 0.17 to 0.63) versus 0.18 (95% CI 0.10 to 0.27); hsp 90, 0.37 (95% CI 0.18 to 0.57) versus 0.22 (95% CI 0.16 to 0.29)). The eight patient s with cystic fibrosis with arthritis had higher anti-hsp 27 antibodie s (0.48 (95% CI 0.13 to 0.92)) than the 42 patients without arthritis (0.22 (95% CI 0.17 to 0.30)). Conclusions - These findings suggest tha t the arthritis associated with cystic fibrosis, despite being seroneg ative for rheumatoid factor, was associated with more severe lung dise ase and with a greater inflammatory response to heat shock proteins.