Anti-interferon-γ autoantibody syndrome mimicking lymphoproliferative disorders: a case series

Anti-interferon-γ autoantibody (AIGA) syndrome is an emerging adult-onset immunodeficiency strongly associated with disseminated opportunistic infections, particularly non-tuberculous mycobacteria (NTM). Its initial manifestations - fever, lymphadenopathy and constitutional symptoms- are not specific and may resemble lymphoproliferative disorders. We describe two patients who presented with prolonged fever, weight loss and generalized lymphadenopathy. Excisional lymph node biopsies initially suggested multicentric Castleman disease (MCD) in one patient and angioimmunoblastic T-cell lymphoma (AITL) in the other, leading to a presumptive diagnosis of lymphoproliferative disease. Both patients were subsequently found to have disseminated dual NTM infections (Mycobacterium abscessus and Mycobacterium kansasii) and neutralizing anti-interferon-γ autoantibodies with inhibition of signal transducer and activator of transcription 1 (STAT1) phosphorylation on flow cytometry, confirming AIGA syndrome. Both cases were given antimycobacterial therapy, with the first case also receiving rituximab immunomodulatory therapy, achieving good clinical and radiological response. These two cases highlight the significant clinical and histological overlap between AIGA syndrome and lymphoproliferative disorder, and emphasize the importance of microbiology evaluation of biopsied tissue and immunological evaluation. AIGA syndrome should be considered in patients with unexplained fever and lymphadenopathy, particularly in Southeast Asia, when biopsy cultures yield non-tuberculous mycobacteria.