Efficacy of bortezomib for treating anti-interferon-gamma autoantibody-associated adult-onset immunodeficiency (AOID) syndrome

Abstract Background There is currently no effective treatment for adult-onset immunodeficiency (AOID) syndrome with anti-interferon-gamma autoantibodies (anti-IFN-γ-auto-Abs). The purpose of this study is to investigate the effectiveness of bortezomib (BTZ) for decreasing anti-IFN-γ-auto-Abs.‏ Methods A pre-and post-intervention study was conducted during February 2017-June 2019 at Siriraj Hospital (Bangkok, Thailand).‏ Five patients were invited to receive once weekly BTZ (1.‏3 mg/m2 body surface area) subcutaneously for 8 weeks followed by oral cyclophosphamide (1 mg/kg/day) for 4 months.‏ The primary outcomes were the difference in antibody level at 8 and 48 weeks compared to baseline, and the incidence of serious adverse events (AEs).‏ The secondary outcome was the occurrence of opportunistic infections (OIs) throughout 72 weeks after starting BTZ.‏ Results The median patient age was 46 years (range: 34-53).‏ All patients had 3-5 OIs prior to enrollment.‏ All patients were receiving antimycobacterial agents for treatment of nontuberculous mycobacterial infection at enrollment.‏ There was no significant difference in the mean optical density of auto-Abs at 8 weeks (3.‏73 ± 0.‏72) or 48 weeks (3.‏74 ± 0.‏53) compared to baseline (3.‏84 ± 0.‏49) (p = 0.‏336 and p = 0.‏555, respectively).‏ However, after serum dilution, the antibody titer non-significantly decreased during 8-16 weeks after BTZ initiation (p = 0.‏345).‏ Ten OIs were observed during 24-72 weeks after BTZ initiation, and Mycobacterium abscessus was the most prevalent pathogen.‏ Conclusions Treatment with BTZ followed by cyclophosphamide yielded no significant decrease in antibody titer levels, and ten OIs were observed during 24-72 weeks of BTZ.‏ No serious AEs were observed.‏ Combining rituximab with BTZ is likely necessary to prevent generation of new autoantibody-producing plasma cells.‏