Antibodies to carbonic anhydrase in systemic lupus erythematosus and other rheumatic diseases.
OBJECTIVE
Autoantibodies to CA were demonstrated in the sera of patients with systemic lupus erythematosus (SLE) and some other rheumatic diseases. This study was undertaken to define the isoform and species specificity of these reactions, as well as to develop a method for detecting immune complexes.


METHODS
Antibodies to CA were sought by enzyme-linked immunosorbent assay (ELISA) and by Western immunoblotting.


RESULTS
An increased prevalence of CA autoantibodies was detected, by both methods, in patients with SLE, scleroderma, and polymyositis, compared with controls. In SLE patients, CA autoantibodies occurred preferentially in those with anti-U1 RNP or anti-U1 RNP and Ro/SS-A. Some sera reacted with only the CA I or CA II isoform, while approximately 50% of sera that were CA positive reacted with both isoforms. The autoantibodies reacted preferentially with the human enzymes, rather than the bovine CA, both on Western blot and by ELISA: Selected IgG F(ab')2 fragments from anti-CA-containing sera specifically inhibited the enzyme activity of CA, and the CA inhibitor acetazolamide partially inhibited the binding of anti-CA to CA. Thus, at least a part of autoanti-CA is directed toward the active site of CA. Finally, CA molecules were detected as immune complexes in sera from selected anti-CA-positive patients.


CONCLUSIONS
Autoantibodies to CA represent a previously unrecognized autoantibody to an abundant intracellular protein of the human erythrocyte.
Itoh
Y
Y
Oklahoma Medical Research Foundation, Department of Medicine, College of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City 73104.
Reichlin
M
M
D000086:Acetazolamide / Q000494:pharmacology; D000918:Antibody Specificity; D000936:Antigen-Antibody Complex / Q000032:analysis; D000937:Antigen-Antibody Reactions / Q000187:drug effects; D001323:Autoantibodies / Q000032:analysis* / Q000276:immunology; D001324:Autoantigens / Q000032:analysis; D015153:Blotting, Western; D002256:Carbonic Anhydrases / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000502:physiology; D007527:Isoenzymes / Q000276:immunology / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D008297:Male; D009220:Myositis / Q000097:blood / Q000276:immunology; D020733:RNA, Small Cytoplasmic; D012216:Rheumatic Diseases / Q000097:blood / Q000276:immunology*; D012261:Ribonucleoproteins / Q000276:immunology; D017411:Ribonucleoproteins, Small Nuclear; D012595:Scleroderma, Systemic / Q000097:blood / Q000276:immunology; D000099207:SS-A Antigen
D000086:Acetazolamide; D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D001324:Autoantigens; D002256:Carbonic Anhydrases; D007140:Immunoglobulin Fab Fragments; D007527:Isoenzymes; D020733:RNA, Small Cytoplasmic; D012261:Ribonucleoproteins; D017411:Ribonucleoproteins, Small Nuclear; D000099207:SS-A Antigen; C116006:RO60 protein, human