Loss of interferon-γ (IFN-γ) function through the development of neutralizing autoantibodies results in a late-onset immunodeficiency characterized by disseminated opportunistic infection. While rare, there is a higher prevalence in patients of Southeast Asian ancestry. Treatment is aimed at B cell depletion; however, relapse is common. Here we describe two cases of anti–IFN-γ autoantibody-associated immunodeficiency.
Patient 1: A 42-year-old female originally from Laos presented with a 30-lb weight loss and fatigue over the course of 8 months. Cultures grew Mycobacterium hassiacum. Testing by National Jewish was positive for anti–IFN-γ autoantibody via ELISA and for IFN-γ neutralizing ability via pSTAT1 phosphorylation. Autoantibodies were treated with rituximab 375 mg/m2 weekly for 4 weeks. She had subsequent negative autoantibody levels for 6 months until positive autoantibodies were again detected. She was treated with an additional 3 rituximab 375 mg weekly infusions and maintained remission for an additional 15 months until autoantibody levels were again positive without associated symptoms or infection (see table for timeline). She is currently undergoing additional 4 rituximab infusions.
A 59-year-old female originally from Laos who presented for an immunodeficiency workup with a history of disseminated Mycobacterium avium infection, with pulmonary, lymph node, and parotid gland involvement. Anti–IFN-γ autoantibody testing from National Jewish was positive. She was treated with rituximab 375 mg/m2 weekly for 4 weeks. Autoantibody levels were negative 3 months later, and she has maintained remission since by serial monitoring.
In our experience, anti–IFN-γ autoantibody-associated secondary immunodeficiency should be suspected in middle-aged patients with disseminated opportunistic infection, especially women of Southeast Asian ancestry. Rituximab rapidly depletes autoantibody levels; however, maintenance of remission is variable. The average duration of response in patient 1 was 10.5 months compared with persistent remission in patient 2. Thus, serial monitoring with autoantibody levels, markers of inflammation, and symptom assessments should be performed with consideration for repeated doses of rituximab.
