Therapeutic modalities and clinical outcomes in a large cohort with LRBA deficiency and CTLA4 insufficiency
Makaleler > Tam Makale · 2023
Yazarlar: Nigar Taghizade, Royala Babayeva, Altan Kara, Ibrahim Serhat Karakus, Mehmet Cihangir Catak, Alper Bulutoglu, Zehra Sule Haskologlu, Idil Akay Haci, Ceyda TUNAKAN DALGIÇ, Esra Karabiber, Sevgi Bilgic Eltan, Melek Yorgun Altunbas, Asena Pinar Sefer, Ahmet Sezer, Sefika Ilknur Kokcu Karadag, Elif Arik, Zuhal Karali, Aylin Ozhan Kont, Can Tuzer, Sait Karaman, Selver Seda Mersin, Nurhan Kasap, Enes Celik, Dilara Fatma Kocacik Uygun, Sezin Aydemir, Ayca Kiykim, Cigdem Aydogmus, Esra Ozek Yucel, Fatih Celmeli, Emrah Karatay, Emine Bozkurtlar, Semra Demir, Ayse Metin, Neslihan KARACA, Necil KÜTÜKÇÜLER, Güzide AKSU, Sukru Nail Guner, Sevgi Keles, Ismail Reisli, Yasemin Kendir Demirkol, Tugba Arikoglu, Nesrin Gulez, Ferah Genel, Sara Sebnem Kilic, Caner Aytekin, Ozlem Keskin, Alisan Yildiran, Dilek Ozcan, Derya Ufuk Altintas, Fatma Omur Ardeniz, Esin Figen Dogu, Kamile Aydan Ikinciogullari, Elif Karakoc-Aydiner, Ahmet Ozen, Safa Baris
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, SCI Expanded İndekslerine Giren Dergi, Uluslararası, Scopus, 2023, cilt 152, ss 1634-1645
DOI: 10.1016/j.jaci.2023.08.004
Özet
Background: 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. Objective: 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. Methods: 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. Results: 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. Conclusions: 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.