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Treatment of Anti-Interferon-Gamma Autoantibody Associated Acquired Immunodeficiency Syndrome with Bortezomib : Pilot study

ณสิกาญจน์ อังคเศกวินัย; Nasikarn Angkasekwinai; ยุพิน ศุพุทธมงคล; Yupin Suputtamongkol; มานพ พิทักษ์ภากร; Manop Pithukpakorn; วันรัชดา คัชมาตย์; Wanruchada Katchamart; เอกพันธ์ ครุพงศ์; Ekkapun Karuphong; ภาคภูมิ พุ่มพวง; Pakpoom Phoompoung; ณัฐวัฒน์ อ่อนลมูล; Nattawat Onlamoon; พรพิมล อังคเศกวินัย; Pornpimon Angkasekwinai;
Date: 2563
Abstract
Background: Adult-onset immunodeficiency syndrome (AOIS) due to anti-interferon-gamma (IFN-ϒ) autoantibodies has emerged in otherwise immunocompetent adults. Currently there is no specific treatment for the diseases. Immunosuppressive agents to inhbit antibody production are the mainstay treatment of several autoimmune diseases. This study aims to evaluate the effectiveness of bortezomib in decreasing level of autoantibodies (Abs) in patients with anti-IFN-ϒ auto-Abs. Methods: A pilot pre-and postintervention study of patients with anti-IFN-ϒ auto-Abs was conducted between February 2017 and June 2019 at Faculty of Medicine Siriraj Hospital. Five patients with high titer of anti-IFN-ϒ auto-Abs were selected to receive bortezomib at the dose of 1.3 mg/m2 body surface area (BSA) once weekly for a total of 8 weeks and cyclophosphamide at the dose of 1 mg/kg/day for the following 4 months. The primary outcome was the difference of autoanibody level at 8 and 48 weeks compared to baseline and any adverse event occurred during the study period. The clinical characteristics, the number of opportunistic infections (OIs) within 72 weeks of study enrollment and the inflammatory biomarker such as C-reactive protein or erythrocyte sedimentation rate were also evaluated. Results: A total 5 patients were enrolled, of which the median age was 46 years (34-53 years) and 2 patients were male. All patients had 3-5 OIs before enrollment. There was no significant difference in the mean (+SD) optical density (OD) values of autoantibody at 8 weeks (3.73 + 0.72) and 48 weeks (3.74 + 0.53) compared to baseline (3.84 + 0.49) (p=0.336 and p=0.555, respectively). No recurrence of infection was observed in the first 6 months. However, during the 72 weeks of follow-up, 4 of 5 cases had a total of 10 recurrent OIs of which Mycobacterium abscessus was the most common. Infection with Talaromyces marneffei was observed in 3 patients at approximately 1 year after bortezomib administration. Conclusions: Bortezomib appears unable to reduce autoantibody in patients with anti-IFN-ϒ auto-Abs. Although no recurrent infection was observed within the first 6 months during the study medication, recurrent OIs were observed thereafter. Bortezomib seems to increase risk of infection with T. marneffei. Long term follow-up should be considered in patients with anti-IFN-ϒ auto-Abs who received immunosuppressive agents.
Copyright ผลงานวิชาการเหล่านี้เป็นลิขสิทธิ์ของสถาบันวิจัยระบบสาธารณสุข หากมีการนำไปใช้อ้างอิง โปรดอ้างถึงสถาบันวิจัยระบบสาธารณสุข ในฐานะเจ้าของลิขสิทธิ์ตามพระราชบัญญัติสงวนลิขสิทธิ์สำหรับการนำงานวิจัยไปใช้ประโยชน์ในเชิงพาณิชย์
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