The thyroid microsomal antibody (M-Ab) has been found to be an antibody against
thyroid peroxidase (TPO), and such
antibodies have been reported not only to bind TPO but also to directly inhibit TPO activity. In this study we investigated the relationship between TPO activity-inhibiting
immunoglobulin (TPII) and thyroid function in 55 untreated patients with
hyperthyroidism due to
Graves' disease and 35 untreated patients with
Hashimoto's disease. TPO partially purified from the microsomal fraction of Graves' thyroid tissue by Sephacryl S-300 gel filtration was incubated with
immunoglobulin (Ig) fractions of serum prepared by precipitation with 15%
polyethylene glycol. At the end of incubation, TPO activity was measured by a
guaiacol assay. The TPII level was expressed as the TPII index, defined as the inhibition of TPO activity by patient Ig divided by inhibition produced by a known positive Ig. We also measured serum free T4, free T3, and TSH concentrations and anti-M-Ab titers, the latter by a microenzyme-linked
immunosorbent assay. When a positive TPII index was defined as more than the mean + 2 SD of the TPII index (0.38) for 15 normal subjects, 13 patients with
Graves' disease and 14 patients with
Hashimoto's disease had positive TPII index values. There was a positive correlation between the TPII index values and the M-Ab titers in patients with either
Graves' disease (r = 0.38; P less than 0.01) or
Hashimoto's disease (r = 0.52; P less than 0.01). The mean TPII index in patients with
Hashimoto's disease was significantly higher than that in patients with
Graves' disease [0.38 +/- 0.42 (+/- SD) vs. 0.19 +/- 0.41; P less than 0.05]. The slope of the regression line between the TPII index values and the M-Ab titers for patients with
Hashimoto's disease was steeper than that for patients with
Graves' disease. The mean serum free T4 concentration was significantly lower in those patients with
Hashimoto's disease who had positive TPII index values than in those with negative TPII index values (14.0 +/- 5.0 vs. 9.6 +/- 3.7 pmol/L; P less than 0.01). There was no significant difference in thyroid function between the patients with
Graves' disease with positive and negative TPII index values. TPII appears to inhibit thyroid function in some patients, but no simple relationship between TPII and thyroid function in autoimmune
thyroid disease was demonstrated. Understanding the factors that control access of anti-TPO antibody to its
antigen may help to elucidate the significance of circulating anti-TPO antibody.