Detailed analysis demonstrated that loss-of-function mutations in OTULIN and accumulation of M1-polyUb levels in myeloid cells in a TNF-dependent manner recapitulate the severe phenotypes of inflammation and autoimmunity observed in ORAS patients, which however can be ameliorated by treatment with the anti-TNF neutralizing antibody Infliximab144. The gene discussed is OTULIN; the disease is autoinflammation, panniculitis, and dermatosis syndrome, autosomal recessive.