FALSE-NEGATIVE RESULTS OBSERVED IN ANTITHYROID PEROXIDASE AUTOANTIBODY DETERMINATION BY COMPETITIVE RADIOIMMUNOASSAYS USING MONOCLONAL-ANTIBODIES

Objective: Anti-thyroid peroxidase autoantibody (anti-TPO) and anti-th yroid microsomal antibody (anti-M) are strictly related, but discrepan cies are sometimes observed. The aim of this study was to assess the i ncidence and to identify the causes of these discrepancies. Design and antibody measurements: Anti-M by passive hemagglutination and anti-TP O by two competitive monoclonal antibody-assisted radioimmunoassays (R IA-1 and RIA-2) were measured in 10 103 sera from 4232 subjects (663 m ale, 3569 female) screened for thyroid disease. Results: Anti-TPO and anti-M correlated quite well (r = 0.7 and p < 0.0001 by RIA-1; r = 0.7 4 and p < 0.0001 by RIA-2), with discrepancies mostly limited to sera with low antibody titers. After exclusion of the latter samples, anti- TPO were detected in only 79 (1.4%) out of 5317 anti-M negative sera, but were undetectable in a more consistent proportion (130/2880 = 4.5% ) of sera from patients with autoimmune thyroid disease and positive a nti-M. In 61 sera of the latter group, anti-TPO was measured by a non- competitive RIA (RIA-3). Forty-one (67.7%) were positive by RIA-3, sug gesting the presence of anti-TPO not competing with the monoclonal ant ibodies of RIA-1 and RIA-2. The remaining 20 sera had undetectable ant i-TPO also by RIA-3. Nineteen (95%) of these sera had positive anti-th yroglobulin (anti-Tg) autoantibody and preincubation with thyroglobuli n inhibited the agglutination reaction of anti-M tests. Conclusion: An ti-TPO by competitive monoclonal antibody-assisted RIA is negative in a minority of sera of patients with autoimmune thyroid disease and pos itive anti-M. This could be accounted for by anti-Tg producing false p ositives in the anti-M assay and by a subset of anti-TPO not competing with the monoclonal antibodies in the RIA. When autoimmune thyroid di sease is suspected on clinical grounds, a negative anti-TPO test with a competitive RIA should be confirmed always by a non-competitive assa y.