An overview of HLA variants in COVID-19 vaccine-induced autoimmunity

COVID-19 vaccination, both in healthy individuals and those with comorbid medical disorders, has proven highly effective in mitigating critical disease progression and mortality rates. Nevertheless, although rare, induction of autoantibodies and new-onset autoimmune conditions in apparently healthy individuals receiving COVID-19 vaccination have been documented. These autoimmune phenomena can be broadly classified into organ-specific autoimmune disorders (e.g., subacute thyroiditis (SAT)) and systemic autoimmune disorders, with many being generally transient (e.g., vaccine-induced thrombotic thrombocytopenia (VITT)) and others causing chronic disability (e.g., systemic vasculitis). Recent studies have highlighted significant associations between COVID-19 vaccine-associated autoimmunity and human leukocyte antigen (HLA) loci. For example, HLA class I alleles such as HLA-B*35 and HLA-C*04 have been associated with COVID-19 vaccine-induced SAT, while HLA class II alleles, including HLA-DRB1*11:04, HLA-DQA1*05:01, HLA-DQB1*02:01, and HLA-DPB1*17:01, have been linked to VITT. This review synthesizes the reported associations between classical HLA loci and COVID-19 vaccine-induced autoimmunity, providing insights into potential mechanisms and clinical implications.