Elevated IgG Antibody Levels to the Mycobacterial 65‐kDa Heat Shock Protein Are Characteristic of Patients with Rheumatoid Arthritis

We have previously demonstrated raised levels of IgG and IgA antibody to the mycobacterial 65‐kDa heat shock protein (hsp) in the sera of patients with rheumatoid arthritis (RA). We have now attempted to determine whether this phenomenon is specific for RA, and whether it is seen only with the mycobacterial homologue of this particular hsp gene family. We therefore screened antibody levels to the mycobacterial and Escherichia coli hsp 65, and the mycobacterial, E. coli, and human hsp 70, in sera from RA, systemic lupus erythematosus (SLE), tuberculosis (TB), ankylosing spondylitis (AS), Crohn's disease, and control donors. RA sera show the greatest increase in IgA binding to the mycobacterial hsp65, but no increase in IgA binding to the E. coli homologue. Similarly, only RA and TB sera show increased IgG binding to the mycobacterial hsp65, and we have shown previously that the titre is greater in RA. In contrast, the use of mycobacterial and E. coli hsp70 preparations as control bacterial hsp gene products has shown that RA patients do not differ from TB or SLE patients in their antibody binding to these proteins. Moreover, neither IgA nor IgG antibody to the human hsp70 in RA sera were higher than in TB, and the IgA binding was not higher than in SLE. These findings suggest that elevated IgG antibody levels to the mycobacterial hsp65 shows some disease specificity, and further studies with the human homologue and at the T‐cell level are required.

[1]  G. Rook,et al.  The use of antigen-bearing nitrocellulose particles derived from Western blots to study proliferative responses to 27 antigenic fractions from Mycobacterium leprae in patients and controls. , 1989, Immunology.

[2]  D. Isenberg,et al.  Raised serum IgG and IgA antibodies to mycobacterial antigens in rheumatoid arthritis. , 1989, Annals of the rheumatic diseases.

[3]  D. Young,et al.  Biochemical and antigenic characterization of the Mycobacterium tuberculosis 71 kD antigen, a member of the 70 kD heat‐shock protein family , 1989, Molecular microbiology.

[4]  G. Bahr,et al.  HLA-DR and tuberculin tests in rheumatoid arthritis and tuberculosis. , 1989, Annals of the rheumatic diseases.

[5]  G. Rook,et al.  Antibody levels to mycobacteria in relation to HLA type: evidence for non-HLA-linked high levels of antibody to the 65 kD heat shock protein of M. bovis in rheumatoid arthritis. , 1988, Clinical and experimental immunology.

[6]  D. Symmons,et al.  Development and Assessment of a Computerized Index of Clinical Disease Activity in Systemic Lupus Erythematosus , 1988 .

[7]  F. Breedveld,et al.  SYNOVIAL FLUID T CELL REACTIVITY AGAINST 65 kD HEAT SHOCK PROTEIN OF MYCOBACTERIA IN EARLY CHRONIC ARTHRITIS , 1988, The Lancet.

[8]  T. Pincus,et al.  HLA-DR4 and other genetic markers in rheumatoid arthritis. , 1988, British journal of rheumatology.

[9]  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.

[10]  B. Polla, A role for heat shock proteins in inflammation? , 1988, Immunology today.

[11]  G. Blobel,et al.  70K heat shock related proteins stimulate protein translocation into microsomes , 1988, Nature.

[12]  Elizabeth A. Craig,et al.  A subfamily of stress proteins facilitates translocation of secretory and mitochondrial precursor polypeptides , 1988, Nature.

[13]  G. Bahr,et al.  HLA-DR-associated isotype-specific regulation of antibody levels to mycobacteria in rheumatoid arthritis. , 1988, Clinical and experimental immunology.

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

[15]  A. Kolk,et al.  Characterization, sequence determination, and immunogenicity of a 64-kilodalton protein of Mycobacterium bovis BCG expressed in escherichia coli K-12 , 1987 .

[16]  C. Georgopoulos,et al.  Purification and properties of the groES morphogenetic protein of Escherichia coli. , 1986, The Journal of biological chemistry.

[17]  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.

[18]  W. Eden,et al.  EVIDENCE FOR AN HLA-DR4-ASSOCIATED IMMUNE-RESPONSE GENE FOR MYCOBACTERIUM TUBERCULOSIS A Clue to the Pathogenesis of Rheumatoid Arthritis? , 1986, The Lancet.

[19]  R. Dwek,et al.  Association of rheumatoid arthritis and primary osteoarthritis with changes in the glycosylation pattern of total serum IgG , 1985, Nature.

[20]  I. Cohen,et al.  Arthritis induced by a T-lymphocyte clone that responds to Mycobacterium tuberculosis and to cartilage proteoglycans. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[21]  D. Isenberg,et al.  Multiple serologic reactions and their relationship to clinical activity in systemic lupus erythematosus. , 1984, Arthritis and rheumatism.

[22]  A. Young,et al.  The clinical assessment of joint inflammatory activity in rheumatoid arthritis related to radiological progression. , 1980, Rheumatology and rehabilitation.

[23]  E. Craig,et al.  The heat shock response. , 1985, CRC critical reviews in biochemistry.