It remains to be determined whether potential defects in early B cell tolerance checkpoints in ICU patients with ACA result from genetic alterations, such as autoimmune regulator (AIRE) deficiency in patients with APS-1, promoting sustained serum ACA over time, or if these B cell tolerance defects are only transiently induced during infection. The gene discussed is AIRE; the disease is Autoimmune polyendocrinopathy type 1.