Epitope recognition patterns of thyroid peroxidase autoantibodies in healthy individuals and patients with Hashimoto's thyroiditis*

Abstract

Thyroid peroxidase antibodies (TPOAb) are markers of autoimmune thyroid disease (AITD), including Hashimoto's thyroiditis (HT), but naturally occurring TPOAb are also detectable in healthy, euthyroid individuals. In AITD, circulating TPOAb react mainly with two immunodominant regions (IDR), IDR-A and IDR-B. The present study was undertaken in order to compare the epitope recognition pattern of TPOAb in HT patients and healthy subjects. Sera from 21 out of 98 healthy controls were selected on the basis of high TPOAb values, required for determination of TPOAb recognition pattern; as were sera from 92 HT patients. Measurement of IDR-reactivity was possible in 90 patients and 12 controls. IDR-A-, IDR-B- and non-IDR-A/non-IDR-B-Ab constituted 24 +/- 11%, 50 +/- 15% and 26 +/- 12%, respectively, in the patients. The distribution in the controls was distinctly different, only 12 +/- 13% being directed against IDR-A (P < 0.002) and 66 +/- 22% against IDR-B (P < 0.002). Half of the healthy individuals, vs. none of the HT patients, lacked IDR-A reactivity completely (P < 0.0001). In HT patients, IDR-B-Ab proportions increased slightly with increasing TPOAb levels (P < 0.05), while IDR-B-Ab of the controls showed a strong opposite trend (P < 0.0001). Accordingly, the proportion of non-A/non-B-Ab correlated with TPOAb levels in the healthy controls (P < 0.008), and an inverse correlation was seen in HT patients (P < 0.02). The data suggest that TPOAb do not differ only in quantity between HT patients and healthy individuals, but may also follow distinct qualitative patterns. Larger studies are required to confirm this, and to determine whether the propensity to produce antibodies to certain TPO epitopes, for example, IDR-A, is of pathogenic relevance.