A classification of Hashimoto's thyroiditis based on immunohistochemistry for IgG4 and IgG

Abstract

Background: Hashimoto's thyroiditis (HT) is a common organ-specific autoimmune disease. Antithyroglobulin antibodies (TgAb) and antithyroperoxidase antibodies (TPOAb), predominantly of the immunoglobulin (Ig) G class, are hallmarks of HT. It has been reported that HT can be divided into IgG4 and non-IgG4 thyroiditis. The aim of our study was to investigate the meaning of this classification.

Methods: Thyroid sections from 53 Hashimoto's patients with stored serum samples were collected to detect IgG4, IgG, α-smooth muscle actin, and transforming growth factor-β1 expression by immunohistochemical staining. The degree of fibrosis of thyroid parenchyma was qualitatively evaluated by Masson's trichrome. Serum total IgG, IgG4, TPOAb IgG, TgAb IgG, TPOAb IgG4, and TgAb IgG4 were detected by enzyme-linked immunosorbent assays (ELISAs).

Results: Based on immunohistochemistry for IgG4 and IgG, 12 cases of IgG4-positive HT and 41 cases of IgG4-negative HT were identified in our study. The patients in the IgG4-positive HT group were significantly younger than those in the IgG4-negative HT group (p=0.023), and no significant differences were found in sex distribution, disease duration, and distribution of thyroid functional status between these two groups. The degree of fibrosis evaluated by Masson's trichrome and the immunohistochemical expression score of TGF-β1 in the IgG4-positive HT were significantly higher than those in the IgG4-negative HT (p<0.05). No significant differences were found in the levels of serum IgG4, total IgG, or IgG4/IgG ratio. However, TPOAb IgG4 and TgAb IgG4 levels and the ratios of TPOAb IgG4/TPOAb IgG, TgAb IgG4/TgAb IgG, TPOAb IgG4/IgG4, and TgAb IgG4/IgG4 were significantly higher in the IgG4-positive HT group than those in the IgG4-negative HT group respectively (p<0.05).

Conclusions: Our study indicates that HT can be divided into IgG4-positive and IgG4-negative HT, and this classification might have important clinical implications. The levels of IgG4 binding to specific thyroid antigens might be noninvasive markers to differentiate these two different immunophenotypes.