Liu H, Perugino CA, Ghebremichael M, et al. - In a clinically diverse cohort of IgG4-related disease (IgG4-RD) individuals (n = 100), via ELISA, autoantibody responses against prohibitin, annexin A11, and laminin 511-E8 were measured in order to examine the role of the adaptive immune response in IgG4-RD. The relative frequencies of antibody responses against prohibitin, annexin A11, laminin 511-E8 was investigated. These four autoantibodies for association with organ distribution, disease severity and co-occurrence with each other were examined. In only a small proportion of individuals with IgG4-RD, antibodies against prohibitin, annexin A11, and laminin 511-E8 were obtained. A subset of IgG4-RD individuals, nonetheless, had IgG4 antibodies against ≥ 2 autoantigens. Moreover, individuals with antibodies against ≥ 2 autoantigens present with strong IgG subclass rises, complement consumption, and visceral organ involvement. This broader break in immunological tolerance in IgG4-RD was related to more critical disease.