Antibodies to Carbonic Anhydrase in Systemic Lupus Erythematosus and Other Rheumatic Diseases

Abstract

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 1 or CA II isoform, while ˜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. Conclusion. Autoantibodies to CA represent a previously unrecognized autoantibody to an abundant intracellular protein of the human erythrocyte.

Human carbonic anhydrase XII: cDNA cloning, expression, and chromosomal localization of a carbonic anhydrase gene that is overexpressed in some renal cell cancers

“…Serum antibodies to CA I and CA II, both rather widely expressed cytoplasmic CAs, have been described in humans with different autoimmune diseases like Sjögren syndrome, immune cholangiopathies, scleroderma, and systemic lupus erythematosus (20,(53)(54)(55)(56). However, serum antibodies to CAs in tumor patients have not been investigated.…”

Low-Avidity Antibodies to Carbonic Anhydrase-I and -II in Autoimmune Chronic Pancreatitise

“…Since a high prevalence of anti-CA Abs in sera containing anti-SSa/SSb Abs has been described [3,7], we further evaluated the serum titers of anti-CA Abs in 33 serum samples positive for anti-SSa and/or SSb Abs, regardless of the diagnosis. We found 6 of 33 sera (18%) containing anti-CA-I Abs and 11 of 33 (33%) sera positive for anti-CA-II Abs.…”

“…Anti-CA-II autoAbs have been found in PBC that do not have antimitochondrial autoAbs [6]. Those autoAbs have also been described in SS or in systemic lupus erythematosus (SLE) [7].…”

Effect of Anti-Carbonic Anhydrase Antibodies on Carbonic Anhydrases I and II

“…Anti-CA I and anti-CA II antibodies (aCAIab and aCAIIab) have recently been isolated from patients with systemic lupus erythematosus (8,9 ), polymyositis and systemic sclerosis (9 ), endometriosis (10,11 ), Sjö gren syndrome (8,9,12,13 ), idiopathic chronic pancreatitis (13,14 ), primary biliary cirrhosis (PBC) (12,13,15,16 ), and autoimmune cholangitis (15 ).…”

“…According to this hypothesis, it seems that highly active CA isoenzymes (cytosolic CA II and membrane-bound CA IV) are particularly involved, because CA plays an important role in such biochemical processes as tissue hydration and secretory activities. In some cases, the preincubation of CA with specific inhibitors has blocked its antibody interactions, suggesting that the site of the immunologic reaction may involve the active site of the enzyme (9 ).…”