Recognition of human 60 kD heat shock protein by mononuclear cells from patients with juvenile chronic arthritis.
A postulated mechanism for autoimmune disorders is that the immunoreactivity develops against bacterial antigens which show a high degree of sequence homology with mammalian proteins. The mycobacterial 65 kD heat shock protein (hsp) has been implicated in several forms of arthritis. Substantial amounts of the human 60 kD homologue (hsp60) were produced by insertion of the gene into Escherichia coli. To investigate the hypothesis that T-cell reactivity is directed against the endogenous hsp, T-cell proliferation of synovial-fluid and peripheral-blood mononuclear cells in response to hsp60 was studied in samples from six patients with juvenile chronic arthritis (JCA) and nine adult patients with rheumatoid arthritis (RA). There was no T-lymphocyte proliferative response to purified fractions of hsp60 in mononuclear cells from RA patients or healthy children and young adults. However, both synovial-fluid and peripheral-blood mononuclear cells from JCA patients showed substantial proliferative responses. There was a significant correlation between the stimulation indices for human hsp60 and for mycobacterial hsp65 (r = 0.948, p less than 0.02). A similar correlation for hsp60 and mycobacterial hsp70 did not achieve significance. Immunohistochemistry showed that hsp65 and hsp70 homologues were expressed in the synovial membrane in these patients but not in controls. These findings suggest a sequence of events in which hsps become expressed during synovial inflammation and function as autoantigens. In JCA this may be manifested by specific T-cell reactivity which apparently is lost in the more bone-eroding and non-remitting adult disease.
De Graeff-Meeder
E R
ER
Department of Immunology, Het Wilhelmina Kinderziekenhuis, Utrecht, The Netherlands.
van der Zee
R
R
Rijkers
G T
GT
Schuurman
H J
HJ
Kuis
W
W
Bijlsma
J W
JW
Zegers
B J
BJ
van Eden
W
W
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal; D001171:Arthritis, Juvenile / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology; D001324:Autoantigens / Q000494:pharmacology; D002648:Child; D002908:Chronic Disease; D004730:Endothelium, Vascular / Q000166:cytology; D005069:Evaluation Studies as Topic; D005260:Female; D006360:Heat-Shock Proteins / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000494:pharmacology; D013582:Synovial Fluid / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D001324:Autoantigens; D006360:Heat-Shock Proteins; D011994:Recombinant Proteins