Human leukocyte antigens and permanent hypothyroidism after subacute thyroiditis

Subacute thyroiditis (SAT) is a painful, self-limiting thyroid disease. Human leukocyte antigen (HLA) alleles play a significant role in immune system regulation and may influence susceptibility to SAT and viral infections. HLA alleles and other factors that may predispose individuals to post-SAT permanent hypothyroidism (PHT) were investigated.

This retrospective study included 48 patients with SAT and 480 healthy bone‑marrow donor volunteers. The frequencies of HLA alleles in the post-SAT PHT (+) group were compared with those in the post-SAT PHT (-) and control groups. PHT was defined as TSH levels above the reference range (>4.2 μIU/mL) in at least two measurements over 6 months. Next-generation sequencing was performed for HLA-A, -B, -C, -DRB1, and -DQB1.

A CRP level above 32.97 mg/L (p = 0.016) at diagnosis and third-month TSH levels above 2.455 μIU/mL (p = 0.005) were clinical risk factors for post-SAT PHT. The frequency of the HLA-C * 15:02 allele was significantly higher in the post-SAT PHT (+) patients than in the post-SAT PHT (-) patients (p = 0.007), and the frequencies of the HLA-B * 44:02 and HLA-C * 04:01 alleles were higher in the post-SAT PHT (+) patients than in the control group (p = 0.007 and p = 0.010, respectively). Female sex, HLA-B * 18:01, -B * 44:02, and -DRB1 * 4:03 alleles were statistically significant potential predictors for post-SAT PHT in the multivariable logistic regression analysis (p = 0.013, p = 0.004, p = 0.002, and p = 0.005, respectively).

The current findings indicate a common HLA-linked increased sensitivity to PHT post-SAT; however, further studies are required with larger cohorts and other ethnic groups.