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

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. 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. 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 nonactivated 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, CD161 + CD56bright and CD161 + CD56 + CD16 + subsets, decreased. Increased CD161dim, CD161 + CD56 − CD16 + , and CD57 + NK cell subsets coupled with the decreased expression of NKp30 and NKp46 indicate reconfiguration of the NK cell population and acquisition of adaptive features. Intracellular cytokine production of the lymphocyte subpopulations was significantly low in the patients compared with the control group. We conclude that the immune system in patients with anti-IFN-γ Abs could be exhausted in T cells and be adaptive in NK cells, contributing to the distinct clinicopathologic features.