Serum autotaxin levels are associated with Graves’ disease

• Published in: Endocrine Journal Vol. 66; no. 5; pp. 409 - 422
• Main Authors: Araki, Osamu, Nishikawa, Masako, Aoki, Junken, Igarashi, Koji, Kihara, Shinji, Kano, Kuniyuki, Shimamoto, Satoshi, Kurano, Makoto, Murakami, Masami, Nojiri, Takahiro, Yatomi, Yutaka, Nakawatari, Kazuki
• Format: Journal Article
• Language: English
• Published: Japan The Japan Endocrine Society 01.01.2019; Japan Science and Technology Agency
• Subjects: 3T3-L1 Cells; Adipocytes; Adipocytes - drug effects; Adipocytes - metabolism; Animals; Anti-thyroid drugs; Antithyroid Agents - therapeutic use; Autotaxin; Graves Disease - blood; Graves Disease - drug therapy; Graves' disease; Humans; Hyperthyroidism; Isoforms; Lysophosphatidic acid; Lysophosphatidic acids; Mice; Pathogenesis; Phosphoric Diester Hydrolases - blood; Phosphoric Diester Hydrolases - metabolism; Serum levels; Thyroid diseases; Thyroid gland; Thyroid hormones; Thyroidectomy; Thyroiditis; Thyroiditis - blood; Thyroiditis - drug therapy; Thyroxine; Thyroxine - pharmacology; Triiodothyronine; Triiodothyronine - pharmacology; Lysophosphatidic acids; Thyroid hormones; Graves’ disease; Autotaxin; Anti-thyroid drugs
• ISSN: 0918-8959; 1348-4540; 1348-4540
• DOI: 10.1507/endocrj.EJ18-0451

Graves’ Disease is a representative autoimmune thyroid disease that presents with hyperthyroidism. Emerging evidence has shown the involvement of lysophosphatidic acid (LPA) and its producing enzyme, autotaxin (ATX), in the pathogenesis of various diseases; among them, the involvement of the ATX/LPA axis in some immunological disturbances has been proposed. In this study, we investigated the association between serum ATX levels and Graves’ disease. We measured the levels of serum total ATX and ATX isoforms (classical ATX and novel ATX) in patients with untreated Graves’ disease, Graves’ disease treated with anti-thyroid drugs, patients with subacute thyroiditis, silent thyroiditis, Plummer’s disease, or Hashimoto’s thyroiditis, and patients who had undergone a total thyroidectomy, as well as normal subjects. The serum total ATX and ATX isoform levels were higher in the patients with Graves’ disease, compared with the levels in the healthy subjects and the patients with subacute thyroiditis. Treatment with anti-thyroid drugs significantly decreased the serum ATX levels. The serum ATX levels and the changes in serum ATX levels during treatment were moderately or strongly correlated with the serum concentrations or the changes in thyroid hormones. However, the administration of T3 or T4 did not increase the expression or serum levels of ATX in 3T3L1 adipocytes or wild-type mice. In conclusion, the serum ATX levels were higher in subjects with Graves’ disease, possibly because of a mechanism that does not involve hyperthyroidism. These results suggest the possible involvement of the ATX/LPA axis in the pathogenesis of Graves’ disease.