Antibodies to carbonic anhydrase in endometriosis: Prevalence, specificity, and relationship to clinical and laboratory parameters

Objective: To investigate the presence and clinical association of serum autoantibodies to carbonic anhydrase (CA) in women with and without endometriosis. Design: Sera were tested in an ELISA against human and bovine CAI and/or CAII isoenzymes and by Western immunoblotting of trypsin-digested fragments of human CAII as antigens. The ELISA positivity was defined as mean + 2 SD of 100 control sera. Positive sera also were tested for the presence of antiendometrial antibodies and antinuclear antibodies (ANA) by indirect immunofluorescence assays (IFA) on endometrial(ECC) and HEp-2 cells, antibodies to single-stranded (ss) and double-stranded (ds) DNA by the Farr-type RIA and Crithidia IFA, and extractable nuclear antigens (Sm, nRNP, Ro, and La) by an ELISA. Patients: Sera from 319 patients with laparoscopic diagnosed pelvic endometriosis (100 stage I, 95 stage II, 67 stage III, and 57 stage IV), 100 with other gynecologic disorders, and 100 control women were used. Results: In the ELISA, 113 of 319 (35.4%) endometriosis sera had elevated immunoglobulin G antibodies against nondenatured CA isoenzymes. The reactivity of sera from the endometriosis group was significantly higher (35%) in all four subgroups of patients than each of the nonendometriosis sera (<12% and <6%, respectively). No stage-dependent variation of an autoantibody pattern was evident. However, anti-CA autoantibodies were present in 66.3% of women with endometriosis-associated infertility. The frequency of anti-CA auto antibodies was significantly higher (by 51.7%) in women with antiendometrial antibodies detectable by IFA. In addition, in sera positive for anti-CA. antibodies, the frequency of ANA also was increased (20/113 [17.6%]) with titers of 1:40 to 1:1,080. The ANA-positive sera were negative for anti-ssDNA, anti-dsDNA, anti-Sm, anti-nRNP, and anti-La. However, three sera were positive for anti-Ro antibodies. Immunoblotting study of autoantibody reactivity with trypsin-digested subfragments of human CAII revealed consistent immunoreactivity with 14 to 6.2-kd range CAII peptides. Conclusions: [1] A subgroup of patients with endometriosis have autoantibodies directed to native and linear epitopes of the CA protein. [2] Prevalence of anti-CA antibodies was associated with antiendometrial antibodies and ANA. [3] Anti-CA antibodies were associated with a higher predictive value of the disease when all patient subgroups were considered together.