Prospective Pilot Study of Cyclophosphamide as an Adjunct Treatment in Patients With Adult-Onset Immunodeficiency Associated With Anti-interferon-γ Autoantibodies

Abstract

Background Adult-onset immunodeficiency associated with interferon-γ autoantibody (IGA) is an emerging disease. The majority of patients require both antimicrobial and immunosuppressive treatments. However, anti-CD20 therapy is not fully accessible in a resource-limited setting to date. Background The objectives of this work were to study the efficacy of cyclophosphamide treatment and the role of laboratory biomarkers for disease progression monitoring. Methods A prospective pilot cohort study was conducted among patients with anti-interferon-γ autoantibodies (IGA) who had recurrent infections and required long-term antimicrobial therapy between 2015 and 2018. The patients were categorized into 2 groups: receipt of intravenous cyclophosphamide (IVCY) and receipt of anti-CD20 therapy (RTX). Clinical and laboratory data were determined. Results A total of 17 IGA patients were enrolled. Prolonged fever was the most common manifestation, and the most common infection identified was nontuberculous mycobacterial infections. Both were found in 88.24% of all patients. After completion of IVCY, 9/11 patients achieved complete remission and tended to reach remission faster compared with individuals in the RTX group. The median duration from treatment initiation to remission (interquartile range) was 84 (42–154) days in the IVCY group and 99 (51–202) days in the RTX group. In remission patients, the biomarkers of interest had normalized after treatment, except interferon γ autoantibody titers. There were no differences in adverse events among the 2 groups. Conclusion IVCY may be considered as alternative therapy in this population, especially in resource-limited countries. A comparable clinical outcome to RTX may support its use on a larger scale. However, further study is encouraged.

Clinical findings of Talaromyces marneffei infection among patients with anti-interferon-γ immunodeficiency: a prospective cohort study

“…However, one study reported a significant improvement in clinical symptoms after plasma exchange therapy [ 10 ]. Supplementation of IFN-γ recombinant protein [ 34 ], cyclophosphamide [ 35 , 36 ] and B cell depletion with an anti-CD20 antibody [ 37 , 38 ] have also been successfully used as adjuvant therapies in combination with antimicrobial therapy in a small number of patients. Prospective randomized clinical trials are needed to determine the therapeutic efficiency of these strategies.…”

Talaromyces marneffei and Burkholderia cepacia Co-Infection in a HIV-Uninfected Patient with Anti-Interferon-γ Autoantibodies

“…In previous studies, patients showing progressive or relapsed infections despite at least a 3-month or over 1-year course of intensive antimicrobial therapy were treated with rituximab, and favorable clinical outcomes were achieved. 10 , 11 Our patient had a severe infection and had no significant benefit from antibiotic treatment. We are unsure whether this immunosuppressive drug benefitted the patient or exacerbated the infection.…”

Sweet’s Syndrome Accompanied by Coinfection with Multiple Pathogens and Disseminated Mycobacterium phlei Infection Presenting with Osteolytic Destruction During 12 Years of Follow-Up: A Rare Case Report

“…Several studies have reported that immunosuppressive agents such as anti-CD20 monoclonal antibodies and cyclophosphamide can effectively reduce AIGA titers and have achieved favorable clinical outcomes in patients with refractory NTM infections. 22 , 23 However, the detection of AIGAs in the patient serum was not considered until March 2016, when the patient was finally confirmed to have high titers of AIGAs. Furthermore, the patient showed a good response to anti-NTM therapy in 2016, so she did not receive immunotherapy for AIGAs throughout the clinical course.…”