Lower proportion of intra-thyroidal B lymphocytes CD20+ associated to methimazole and lack of influence of iodide on lymphocyte subpopulations in Graves' disease

Abstract

Graves' disease (GD), an autoimmune thyroid disease, is one of the main autoimmune diseases in the general population. It is known that the pathophysiology of this disease may be related to immunological mechanisms dysregulation. These mechanisms can be influenced by GD therapies, such as iodide or antithyroid drugs (ATD).

Objective

Verify relation between clinical, biochemical and treatment modalities used prior to surgery and histopathological characteristics observed in total thyroidectomy products from patients previously diagnosed with Graves' disease. Furthermore, these data were related to composition of lymphocytic infiltrate in terms of proportions of lymphocytes CD4⁺, CD8⁺, CD25⁺ and CD20⁺. We aim to contribute to the understanding of the evolution pattern of GD, whose pathophysiology is not yet completely understood.

Methods

Cross-sectional study assessing thyroidectomy products for the presence of lymphocytic infiltrate, as well as the proportion and intensity of CD4⁺, CD8⁺, CD25⁺ and CD20⁺ markers. We selected 50 patients who underwent total or partial thyroidectomy in a tertiary service between 1996 and 2013 due to GD with histopathological confirmation. The control group (non-autoimmune disease group) consisted of 12 patients with histopathological data compatible with normal perilesional thyroid parenchyma. The intensity of lymphocytic infiltrate and immunohistochemical expression of the markers CD4⁺ (helper T lymphocytes), CD8⁺ (cytotoxic T lymphocytes), CD25⁺ (regulatory T lymphocytes) and CD20⁺ (B lymphocytes) were retrospectively evaluated and relationship with ultrasound, laboratory and clinical data was assessed.

Results

No differences were found in intensity, presence of lymphoid follicles, and expression of CD4+/CD8+/CD25+ in patients with GD who did or did not use ATD or iodide. In the group that did not use ATD, a higher proportion of CD20⁺ expression was found. The GD group was associated with hyperplastic epithelium and the control group was associated with simple epithelium. There was no difference in ultrasound thyroid volume between the groups. In GD patients with mild lymphocytic infiltrate, higher free thyroxin (FT4) levels were observed than those in patients with no infiltrate or moderate infiltrate.

Conclusion

We found a lower proportion of intrathyroidal CD20⁺ B lymphocytes in patients under use of methimazole. However, no difference was observed in intrathyroidal lymphocyte subpopulations related to the short-term use of iodide. The understanding of thyroid autoimmunity, as well as identifying points of pharmacological modulation, are very important for advancement and improvement in treatments for these diseases.