Clinical course and outcomes of patients with anti-interferon-gamma autoantibody-associated adult-onset immunodeficiency: an observational cohort study.

BACKGROUND: Anti-interferon-gamma autoantibody (anti-IFN-γ-auto-Abs)-associated adult-onset immunodeficiency (AOID) syndrome presents with variable clinical manifestations, and long-term outcome data and natural history remain limited.

MATERIALS AND METHODS: This singlecenter study utilized a disease registry of AOID patients (≥18 years) at Siriraj Hospital, Bangkok, Thailand. Clinical outcomes (survival, death, loss to follow-up) as of November 20, 2024 and disease status (remission, non-remission) at each visit were analyzed.

RESULTS: A total of 65 patients were recorded over an eight-year period between 2017 and 2024. The mean age of all patients was 56.4&#x2009;years, and 66% were female. At initial presentation, 95 opportunistic infections were isolated from 61 patients.(44.2%) was the predominant pathogens, followed bycomplex (13.7%), salmonellosis (9.5%) and(8.4%). Among 53 patients with at least one year of follow-up, 12 (22.6%) achieved remission and 41 (77.4%) remained in non-remission. Antibody levels exhibited a significant decline over time (&#x2009;<&#x2009;0.05) across all patients. However, no significant difference in antibody levels was observed between remission and non-remission group (&#x2009;>&#x2009;0.05). Notably, median baseline and latest antibody concentration were significantly lower in the remission group compared to the non-remission group, respectively (baseline level: 3.5, IQR 2.8-3.8 vs. 4.0, IQR 3.5-4.2,&#x2009;=&#x2009;0.030; latest level: 2.1, IQR 1.8-2.4 vs. 3.0, IQR 2.1-3.6,&#x2009;=&#x2009;0.044).

CONCLUSION: This study noted a slight shift in pathogen distribution, even though rapidly growing mycobacteria remain the most common infection. Most patients experienced non-remission, necessitating prolonged antimicrobial therapy. Our findings indicate a declining trend in antibody levels over time. Given the high rates of non-remission and the associated need for extended treatment, immunomodulatory agents should be considered, especially for non-remission patients, to potentially reduce antibody levels and the risk of infection recurrence.