Clinicopathological Manifestations and Immune Phenotypes in Adult-Onset Immunodeficiency with Anti-Interferon-γ Autoantibodies

Abstract

Purpose Anti-interferon (IFN)-γ autoantibodies (anti-IFN-γ Abs) is an emerging adult-onset immunodeficiency syndrome. Immune dysfunction in this distinct disorder remains to be clarified. Methods We prospectively collected blood samples of 20 patients with anti-IFN-γ Abs and 40 healthy normal subjects. The percentages of lymphocyte subpopulations, most relevant to T, B, and NK cells, and the percentages of stimulated lymphocytes with cytokine production were assessed using eight-color flow cytometry. The results were adjusted to age and absolute lymphocyte counts. Results Most (85%) patients presented nontuberculous mycobacterial infection. Skin lesions were predominantly manifested by neutrophilic dermatoses. The involved lymph nodes had granulomatous inflammation, except 22.2% showing atypical lymphoid hyperplasia without granuloma formation. The percentages of CD4 + T cells and non-activated subpopulations (recent thymic emigrants and naïve subtypes) decreased significantly with increased expression of activation markers and polarization to differentiated cells. The percentage of NK cells increased, but that of two major NK subpopulations, CD56bright and CD56 + CD16 + subsets decreased. Furthermore, the expression of NKp30 and NKp46 decreased with increased CD57 expression. Intracellular cytokine production of the lymphocyte subpopulations were significantly low in the patients compared with the control group. Conclusion We conclude that the immune system in patients with anti–IFN-γ Abs could be exhausted, contributing to the distinct clinicopathologic features.