Role of heat shock proteins in the pathogenesis of cystic fibrosis arthritis.
BACKGROUND
Arthritis is a well recognised complication of cystic fibrosis. The cause of this arthritis is not yet clear but it is likely to be an immunological reaction to one of the many bacterial antigens to 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 patients with cystic fibrosis, with and without arthritis, and in normal age and sex matched healthy controls were measured. The severity of the cystic fibrosis was assessed by lung function tests and chest radiographs. The nature of the organisms colonising the lungs was determined by 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 antibodies were higher in patients in whom the lungs were colonised with Pseudomonas 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 patients with cystic fibrosis with arthritis had higher anti-hsp 27 antibodies (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 that the arthritis associated with cystic fibrosis, despite being seronegative for rheumatoid factor, was associated with more severe lung disease and with a greater inflammatory response to heat shock proteins.
al-Shamma
M R
MR
West of Scotland Adult Cystic Fibrosis Centre, Department of Respiratory Medicine, Gartnavel General Hospital, Glasgow, UK.
McSharry
C
C
McLeod
K
K
McCruden
E A
EA
Stack
B H
BH
D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000097:blood*; D001168:Arthritis / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D003550:Cystic Fibrosis / Q000150:complications* / Q000378:metabolism; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000276:immunology; D006360:Heat-Shock Proteins / Q000097:blood / Q000276:immunology*; D006801:Humans; D007124:Immunoenzyme Techniques; D007074:Immunoglobulin G / Q000097:blood; D008297:Male
D000906:Antibodies; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D007074:Immunoglobulin G