Taghizade, NigarBabayeva, RoyalaKara, AltanKarakuş, Ibrahim SerhatÇatak, Mehmet CihangirBulutoğlu, AlperHaskoloğlu, Zehra ŞuleHacı, Idil AkayDalgıç, Ceyda TunakanKarabiber, EsraEltan, Sevgi BilgiçAltunbaş, Melek YorgunSefer, Asena PınarSezer, AhmetKaradağ, Sefika Ilknur KökcüArık, ElifKont, Aylin ÖzhanTuzer, CanKaraman, SaitMersin, Selver SedaKasap, NurhanÇelik, EnesUygun, Dilara Fatma KocacıkAydemir, SezinKıykım, AycaAydoğmus, CiğdemYücel, Esra ÖzekÇelmeli, FatihKaratay, EmrahBozkurtlar, EmineDemir, SemraMetin, AyseKaraca, Neslihan EdeerKütükçüler, NecilAksu, GüzideGüner, Şükrü NailKeleş, SevgiReisli, IsmailDemirkol, Yasemin KendirArikoğlu, TuğbaGulez, NesrinGenel, FerahAytekin, CanerKeskin, ÖzlemYıldıran, AlişanÖzcan, DilekAltıntaş, Derya UfukArdeniz, Fatma ÖmürDogu, Esin FigenIkincioğulları, Kamile AydanKarakoç-Aydıner, ElifÖzen, AhmetBarış, Safa2024-12-042024-12-042023-12-050091-6749https://doi.org/10.1016/j.jaci.2023.08.004https://hdl.handle.net/11452/48882Background: LPS-responsive beige-like anchor (LRBA) deficiency (LRBA-/-) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA4) insufficiency (CTLA41/-) 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 CTLA41/-) 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 CTLA41/- 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 , 3 (21.3%) continued to receive immunosuppressants after transplantation. HSCT , 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.eninfo:eu-repo/semantics/closedAccessImmune dysregulationPropensity scoreMutationsPolyendocrinopathyEnteropathyAutoimmunityEndocytosisAbataceptDiseaseProteinInborn errors of immunityLps-responsive beige-like anchorCytotoxic t-lymphocyte-associated antigen-4Immune dysre-gulationNatural historyAbataceptHematopoietic stem cell transplantationScience & technologyLife sciences & biomedicineAllergyImmunologyArticle00113367210000116341645152610.1016/j.jaci.2023.08.004