As observed in chronic autoimmune thyroiditis, these hypothyroidism events may be secondary to: reduced number and/or function of immune regulatory suppressor cells (e.g. CD4+CD25+)57,58; the large diversity of the third complementarity-determining region of T-cell surface antigen receptors creating increased propensity of attacking thyroid tissue59; from Th1 cytotoxic T-cell apoptotic destruction of thyroid tissue60; or loss of self-tolerance61 by direct interaction of anti-PD1-/L1 agents with PD-L1/L2 expressed on normal thyroid tissue62. The gene discussed is CD274; the disease is hypothyroidism.