As not all RA at risk individuals with local ACPA develop RA, Holers et al. discussed in their “mucosal origins hypothesis” that mucosal (IgA) ACPA could have a biologically relevant protective role in normal homeostasis, but that chronic mucosal inflammation and dysbiosis may lead to systemic ACPA expression through multiple potential processes [16]. The gene discussed is CD79A; the disease is rheumatoid arthritis.