Taghizade Nigar, Babayeva Royala, Kara Altan, Karakus Ibrahim Serhat, Catak Mehmet Cihangir, Bulutoglu Alper, Haskologlu Zehra Sule, Akay Haci Idil, Tunakan Dalgic Ceyda, Karabiber Esra, Bilgic Eltan Sevgi, Yorgun Altunbas Melek, Sefer Asena Pinar, Sezer Ahmet, Kokcu Karadag Sefika Ilknur, Arik Elif, Karali Zuhal, Ozhan Kont Aylin, Tuzer Can, Karaman Sait, Mersin Selver Seda, Kasap Nurhan, Celik Enes, Kocacik Uygun Dilara Fatma, Aydemir Sezin, Kiykim Ayca, Aydogmus Cigdem, Ozek Yucel Esra, Celmeli Fatih, Karatay Emrah, Bozkurtlar Emine, Demir Semra, Metin Ayse, Karaca Neslihan Edeer, Kutukculer Necil, Aksu Guzide, Guner Sukru Nail, Keles Sevgi, Reisli Ismail, Kendir Demirkol Yasemin, Arikoglu Tugba, Gulez Nesrin, Genel Ferah, Kilic Sara Sebnem, Aytekin Caner, Keskin Ozlem, Yildiran Alisan, Ozcan Dilek, Altintas Derya Ufuk, Ardeniz Fatma Omur, Dogu Esin Figen, Ikinciogullari Kamile Aydan, Karakoc-Aydiner Elif, Ozen Ahmet, Baris Safa
Department of Pediatrics, School of Medicine, Marmara University, Istanbul, Turkey.
Division of Pediatric Allergy and Immunology, School of Medicine, Marmara University, Istanbul, Turkey; Istanbul Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Istanbul, Turkey; The Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey.
J Allergy Clin Immunol. 2023 Dec;152(6):1634-1645. doi: 10.1016/j.jaci.2023.08.004. Epub 2023 Aug 16.
LPS-responsive beige-like anchor (LRBA) deficiency (LRBA) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA4) insufficiency (CTLA4) are mechanistically overlapped diseases presenting with recurrent infections and autoimmunity. The effectiveness of different treatment regimens remains unknown.
Our aim was to determine the comparative efficacy and long-term outcome of therapy with immunosuppressants, CTLA4-immunoglobulin (abatacept), and hematopoietic stem cell transplantation (HSCT) in a single-country multicenter cohort of 98 patients with a 5-year median follow-up.
The 98 patients (63 LRBA and 35 CTLA4) were followed and evaluated at baseline and every 6 months for clinical manifestations and response to the respective therapies.
The LRBA patients exhibited a more severe disease course than did the CTLA4 patients, requiring more immunosuppressants, abatacept, and HSCT to control their symptoms. Among the 58 patients who received abatacept as either a primary or rescue therapy, sustained complete control was achieved in 46 (79.3%) without severe side effects. In contrast, most patients who received immunosuppressants as primary therapy (n = 61) showed either partial or no disease control (72.1%), necessitating additional immunosuppressants, abatacept, or transplantation. Patients with partial or no response to abatacept (n = 12) had longer disease activity before abatacept therapy, with higher organ involvement and poorer disease outcomes than those with a complete response. HSCT was performed in 14 LRBA patients; 9 patients (64.2%) showed complete remission, and 3 (21.3%) continued to receive immunosuppressants after transplantation. HSCT and abatacept therapy gave rise to similar probabilities of survival.
Abatacept is superior to immunosuppressants in controlling disease manifestations over the long term, especially when started early, and it may provide a safe and effective therapeutic alternative to transplantation.
LPS反应性米色样锚定蛋白（LRBA）缺乏症（LRBA）和细胞毒性T淋巴细胞相关抗原4（CTLA4）功能不全（CTLA4）是机制上重叠的疾病，表现为反复感染和自身免疫。不同治疗方案的有效性尚不清楚。
我们的目的是在一个单一国家的多中心队列中，对98例患者进行为期5年的中位随访，以确定免疫抑制剂、CTLA4免疫球蛋白（阿巴西普）和造血干细胞移植（HSCT）治疗的相对疗效和长期结果。
对98例患者（63例LRBA和35例CTLA4）在基线时以及每6个月进行随访和评估，观察临床表现以及对各自治疗的反应。
LRBA患者的病程比CTLA4患者更严重，需要更多的免疫抑制剂、阿巴西普和HSCT来控制症状。在58例接受阿巴西普作为初始或挽救治疗的患者中，46例（79.3%）实现了持续完全控制，且无严重副作用。相比之下，大多数接受免疫抑制剂作为初始治疗的患者（n = 61）表现为部分或无疾病控制（72.1%），需要额外的免疫抑制剂、阿巴西普或移植。对阿巴西普部分或无反应的患者（n = 12）在接受阿巴西普治疗前疾病活动时间更长，器官受累程度更高，疾病结局比完全反应的患者更差。14例LRBA患者接受了HSCT；9例患者（64.2%）完全缓解，3例（21.3%）移植后继续接受免疫抑制剂治疗。HSCT和阿巴西普治疗产生的生存概率相似。
从长期来看，阿巴西普在控制疾病表现方面优于免疫抑制剂，尤其是早期开始使用时，并且它可能为移植提供一种安全有效的治疗替代方案。
