Autoreactivity to human heat-shock protein 60 predicts disease remission in oligoarticular juvenile rheumatoid arthritis.

OBJECTIVE To determine whether T lymphocyte reactivity to endogenous human hsp60 plays a regulatory role in the course of oligoarticular juvenile rheumatoid arthritis (JRA). METHODS A prospective, longitudinal study of T cell reactivity to HSP in 15 patients with newly diagnosed HLA-B27 negative oligoarticular JRA was performed. Results were compared with those in a group of 20 patients with newly diagnosed polyarticular or systemic JRA or with acute arthritis caused by other systemic diseases or viral infections, as well as with those in a group of 9 healthy control subjects. RESULTS In 86% of the patients with oligoarticular JRA (13 of 15), significant T lymphocyte proliferative responses to hsp60 were found in peripheral blood mononuclear cells and/or synovial fluid mononuclear cells within 3 months after the onset of arthritis. Only 5% of the patients in the rheumatologic disease control group (1 of 20) showed such positivity. All patients with oligoarticular JRA and positive responses to human hsp60 developed a remission of their disease within 12 weeks. During this period of remission, blood samples were taken from 8 patients and showed significantly lower and even negative responses to hsp60, compared with active disease, when all 8 patients had good responses. CONCLUSION The results show that significant proliferative responses to human hsp60 can be found early in the course of oligoarticular JRA. Furthermore, these responses correlate with disease activity in such a manner that T cell reactivity to human hsp60 seems to be associated with disease remission.

[1]  P. Helders,et al.  Juvenile chronic arthritis: T cell reactivity to human HSP60 in patients with a favorable course of arthritis. , 1995, The Journal of clinical investigation.

[2]  W. van Eden,et al.  Activation of T cells recognizing self 60-kD heat shock protein can protect against experimental arthritis , 1995, The Journal of experimental medicine.

[3]  W. van Eden,et al.  Differential mycobacterial 65-kDa heat shock protein T cell epitope recognition after adjuvant arthritis-inducing or protective immunization protocols. , 1994, Journal of immunology.

[4]  S. Albani,et al.  Immune responses to the Escherichia coli dnaJ heat shock protein in juvenile rheumatoid arthritis and their correlation with disease activity. , 1994, The Journal of pediatrics.

[5]  R. Vaughan,et al.  T cell epitope expression of mycobacterial and homologous human 65-kilodalton heat shock protein peptides in short term cell lines from patients with Behçet's disease. , 1993, Journal of immunology.

[6]  W. Welch,et al.  How cells respond to stress. , 1993, Scientific American.

[7]  W. van Eden,et al.  Adjuvant arthritis and immunity to the mycobacterial 65 kDa heat shock protein. , 1992, International immunology.

[8]  W. van Eden,et al.  Two monoclonal antibodies generated against human hsp60 show reactivity with synovial membranes of patients with juvenile chronic arthritis , 1992, The Journal of experimental medicine.

[9]  J. Bijlsma,et al.  Recognition of human 60 kD heat shock protein by mononuclear cells from patients with juvenile chronic arthritis , 1991, The Lancet.

[10]  I. Cohen,et al.  Autoimmunity, microbial immunity and the immunological homunculus. , 1991, Immunology today.

[11]  W. Kuis,et al.  Antibodies to the mycobacterial 65-kd heat-shock protein are reactive with synovial tissue of adjuvant arthritic rats and patients with rheumatoid arthritis and osteoarthritis. , 1990, The American journal of pathology.

[12]  W. van Eden,et al.  Protection against streptococcal cell wall-induced arthritis by pretreatment with the 65-kD mycobacterial heat shock protein , 1989, The Journal of experimental medicine.

[13]  C. Harley,et al.  Primary structure of a human mitochondrial protein homologous to the bacterial and plant chaperonins and to the 65-kilodalton mycobacterial antigen , 1989, Molecular and cellular biology.

[14]  R. Young,et al.  Stress proteins are immune targets in leprosy and tuberculosis. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[15]  I. Cohen,et al.  Cloning of the mycobacterial epitope recognized by T lymphocytes in adjuvant arthritis , 1988, Nature.

[16]  I. Cohen,et al.  T LYMPHOCYTES OF RHEUMATOID ARTHRITIS PATIENTS SHOW AUGMENTED REACTIVITY TO A FRACTION OF MYCOBACTERIA CROSS-REACTIVE WITH CARTILAGE , 1986, The Lancet.

[17]  I. Cohen,et al.  Lines of T lymphocytes induce or vaccinate against autoimmune arthritis. , 1983, Science.

[18]  L. Hightower,et al.  Newcastle disease virus stimulates the cellular accumulation of stress (heat shock) mRNAs and proteins , 1982, Journal of virology.

[19]  J. Baum,et al.  Current proposed revision of JRA Criteria. JRA Criteria Subcommittee of the Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Section of The Arthritis Foundation. , 1977, Arthritis and rheumatism.

[20]  Coghill Nf,et al.  A study of consultants. , 1970 .

[21]  C. Pearson,et al.  Passive Transfer of Adjuvant-induced Arthritis and Allergic Encephalomyelitis in Rats using Thoracic Duct Lymphocytes , 1969, Nature.

[22]  W. van Eden,et al.  Specific immunity as a critical factor in the control of autoimmune arthritis: the example of hsp60 as an ancillary and protective autoantigen. , 1995, Scandinavian journal of rheumatology. Supplement.

[23]  P. Matzinger Tolerance, danger, and the extended family. , 1994, Annual review of immunology.

[24]  I. Cohen Autoimmunity to chaperonins in the pathogenesis of arthritis and diabetes. , 1991, Annual review of immunology.

[25]  I. Cohen,et al.  A cartilage-mimicking T-cell epitope on a 65K mycobacterial heat-shock protein: adjuvant arthritis as a model for human rheumatoid arthritis. , 1989, Current topics in microbiology and immunology.

[26]  S. Lindquist,et al.  The heat-shock proteins. , 1988, Annual review of genetics.