Epidemiology, Seroprevalence, and Clinical Manifestations of Immunodeficiency due to Autoantibody Against Interferon Gamma in Hong Kong

Abstract

Introduction/Project Objectives: Patients with adult-onset immunodeficiency due to autoantibodies against interferon gamma (anti-IFN-γ autoantibodies) may develop disseminated and/or recurrent opportunistic infections, including non-tuberculous mycobacteriosis, non-typhoidal salmonellosis, burkholderiosis, penicilliosis, and herpes zoster. While the condition appears to be especially common among Asians, including Chinese residents in Hong Kong, Taiwan, and mainland China, the seroprevalence rate of anti-IFN-γ autoantibodies among these populations is unknown. Moreover, the full spectrum of infective and non-infective clinical manifestations of this immuondeficiency syndrome is not fully understood. This retrospective case-control analysis aimed to investigate the epidemiology, seroprevalence rate, and clinical manifestations of this emerging immunodeficiency syndrome in Hong Kong. Methods: This study was approved by the Institutional Review Board of The University of Hong Kong/Hospital Authority Hong Kong West Cluster. Archived serum samples from subjects aged ≥18 years, with or without opportunistic infections, were tested by a screening enzyme immunoassay and an IFN-γ spiking assay for the presence of anti- IFN-γ autoantibodies. The patients' clinical data were retrieved from the Hospital Authority Electronic Patient Record (ePR) system and entered into a predesigned database. Comparisons between patient groups were evaluated by the Chi-square test (categorical variables) and Mann-Whitney U-test (continuous variables). All statistical analyses were performed using SPSS18.0 for Windows. P<0.05 was considered statistically significant. Results: 3198 serum samples from 3198 patients were tested. Overall, anti-IFN-γ autoantibodies were detected in 34 serum samples (34/3198, 1.1%) in the screening enzyme immunoassay. These included 11 patients with opportunistic infections including non-tuberculous mycobacteriosis, penicilliosis, non-typhoidal salmonellosis, burkholderiosis, and/or herpes zoster (11/133, 8.3%), 4 subjects aged >65 years without these opportunistic infections (4/783, 0.5%), 14 patients with autoimmune diseases without these opportunistic infections (14/753, 1.9%), and 5 patients with chronic HBV/HCV infection without these opportunistic infections (5/764, 0.7%). The seroprevalence rate of anti-IFN-γ autoantibodies in subjects without opportunistic infections was ~1%, which was significantly lower than that of patients with opportunistic infections (8.3%, P<0.001). Some patients with high-titer serum neutralizing anti-IFN-γ autoantibodies also developed reactive (Sweet's syndrome and lobular panniculitis) and infective dermatoses. Anti-IFN-γ autoantibodies were strongly associated with HLA-DR*15:02/16:02 and HLA-DQ*05:01/05:02 among the affected patients. Conclusions: These findings helped to optimize the diagnostic and treatment protocols for this emerging immunodeficiency syndrome. Routine screening for anti-IFN-γ autoantibodies in asymptomatic patients is unlikely warranted. A working algorithm for the diagnosis and treatment of patients with dermatoses associated with anti-IFN-γ autoantibodies was established. Our non-laborious screening enzyme immunoassay could be adopted by clinical laboratories.