Association of Human Leukocyte Antigen Genotypes with Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine-Induced Subacute Thyroiditis

Abstract

<b><i>Background:</i></b> Despite mass vaccination, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-induced subacute thyroiditis (SAT) is rarely seen as a complication. The reason why some individuals are susceptible to developing vaccine-induced SAT is not known. SAT develops in genetically predisposed individuals who carry specific human leukocyte antigen (HLA) haplotypes. It is unknown whether specific HLA alleles are associated with SARS-CoV-2 vaccine-induced SAT. <b><i>Objective:</i></b> This study compared the HLA profiles of patients with SARS-CoV-2 vaccine-induced SAT to controls, to assess whether there is an association between specific HLA genotypes and development of SAT. The relationship between HLA genotypes and the clinical course of SARS-CoV-2 vaccine-induced SAT was also evaluated. <b><i>Methods:</i></b> A case-control study was conducted in a Turkish tertiary care center. Fourteen patients with SARS-CoV-2 vaccine-induced SAT and 100 healthy controls were included. <i>HLA-A, HLA-B, HLA-C, HLA-DQB1</i>, and <i>HLA-DRB1</i> frequencies were analyzed by next-generation sequencing. <b><i>Results:</i></b> The frequencies of <i>HLA-B*35 and HLA-C*04</i> alleles were significantly higher in SARS-CoV-2 vaccine-induced SAT cohort when compared with controls (<i>HLA-B*35</i>: 13 [93%] vs. 40 [40%], <i>p</i> < 0.001; <i>HLA-C*04</i>: 13 [93%] vs. 43 [43%], <i>p</i> < 0.001, respectively). More severe thyrotoxicosis was seen in patients having <i>HLA-B*35</i> and <i>HLA-C*04</i> homozygous alleles (free thyroxine: 4.47 ng/dL [3.77-5.18] vs. 1.41 ng/dL [1.22-2.63], <i>p</i> = 0.048). Inflammation tended to be more severe in homozygous patients (C-reactive protein: 28.2 mg/dL [13.6-42.9] vs. 4.8 [1.2-10.5], <i>p</i> = 0.07). <b><i>Conclusions:</i></b> The frequencies of <i>HLA-B*35</i> and <i>HLA-C*04</i> alleles were higher in SARS-CoV-2 vaccine-induced SAT compared with controls. Homozygosity for <i>HLA-B*35</i> and <i>HLA-C*04</i> was associated with thyrotoxicosis and a greater inflammatory reaction. Our findings should be confirmed in studies of other populations.