Title : Missed, mistaken, but treatable: Refractory mycobacterium avium complex infection revealing anti interferon-γ autoantibody mediated immunodeficiency
Abstract:
Neutralizing anti–interferon-gamma autoantibodies (anti–IFN-γ AAbs) are an underrecognized cause of adult-onset immunodeficiency associated with disseminated Non Tuberculous Mycobacterial (NTM) infections and frequent diagnostic delay. A 45-year-old woman with systemic lupus erythematosus presented with recurrent dyspnea, fever, and pleuritic chest pain unresponsive to multiple courses of antibiotics and corticosteroids. Imaging demonstrated persistent left lower lobe consolidation, and bronchoscopy confirmed Mycobacterium Avium Complex (MAC). Standard triple therapy was initiated but modified due to a rifampin-induced rash. Given ongoing refractory disease, further immunologic evaluation identified anti–IFN-γ AAbs. Rituximab was initiated and well tolerated. At four months, the patient demonstrated marked clinical and radiographic improvement without further hospitalizations. Anti–IFN-γ AAbs disrupt the IL-12/IFN-γ axis, impairing macrophage activation and intracellular pathogen clearance, thereby driving persistent NTM infection. This entity should be considered in patients with unexplained or treatment-refractory NTM disease. Early recognition is critical, as targeted immunomodulatory therapy can significantly alter clinical outcomes.
