Increase of Circulating CXCL9 and CXCL11 Associated with Euthyroid or Subclinically Hypothyroid Autoimmune Thyroiditis

Abstract

Context: Recently, CXCL9 and CXCL11 have been shown to be involved in autoimmune thyroid disorders; however, no data are present about CXCL9 and CXCL11 circulating levels in thyroid autoimmunity. Objective: Our objective was to evaluate circulating CXCL9 and CXCL11 in autoimmune thyroiditis (AIT). Design and Patients or Other Participants: Serum CXCL9 and CXCL11 have been measured in 141 consecutive patients with newly diagnosed AIT (AIT-p), 70 euthyroid controls, and 35 patients with nontoxic multinodular thyroid. The three groups were similar in gender distribution and age; among the AIT-p, 26% had subclinical hypothyroidism. Results: Serum CXCL9 and CXCL11 levels were significantly (P < 0.0001 for both) higher in AIT-p (143 ± 164 and 121 ± 63 pg/ml, respectively) than in controls (68 ± 37 and 65 ± 19 pg/ml, respectively) or patients with multinodular thyroid (87 ± 43 and 71 ± 20 pg/ml, respectively). Among AIT-p, CXCL9 and CXCL11 levels were significantly higher in patients older than 50 yr or those with a hypoechoic ultrasonographic pattern or with hypothyroidism. In a multiple linear regression model including age, thyroid volume, hypoechogenicity, hypervascularity, TSH, anti-thyroglobulin, and anti-thyroid peroxidase, only age and TSH were significantly (P < 0.05) related to serum CXCL9 or CXCL11 levels. In a multiple linear regression model of CXCL9 vs. age, TSH, and CXCL11, TSH (P = 0.032) and CXCL11 (P = 0.001) were significantly and independently related to CXCL9. Conclusions: We first show that circulating CXCL9 and CXCL11 are increased in patients with thyroiditis and hypothyroidism and are related to each other. These results underline the importance of a Th1 immune attack in the initiation of AIT.