Kiykim, AyçaOgulur, İsmailDursun, EsraDogruel, DilekKaraca, Neslihan EdeerCogurlu, Mujde TubaBilir, Ozlem ArmanCansever, MuratKapakli, HasanBaser, DilekKasap, NurhanKutlug, SeyhanAltintas, Derya UfukAl-Shaibi, AhmadAgrebi, NourhenKara, ManolyaGuven, AylaSomer, AyperAydogmus, CigdemAyaz, Nuray AktayMetin, AyseAydogan, MetinUncuoglu, AysenPatiroglu, TurkanYildiran, AlisanGuner, Sukru NailKeles, SevgiReisli, IsmailAksu, GuzideKutukculer, NecilYilmaz, MustafaKarakoc-Aydiner, ElifLo, BerniceOzan, AhmetChatila, Talal A.Barıs, Safa2022-11-242022-11-242019-12Kiykim, A. vd. (2019). ''Abatacept as a long-term targeted therapy for LRBA deficiency ''. Journal of Allergy and Clinical Immunology-in Practice, 7(8), 2790-2800.2213-21982213-2201https://doi.org/10.1016/j.jaip.2019.06.011https://www.sciencedirect.com/science/article/abs/pii/S221321981930563Xhttp://hdl.handle.net/11452/29557BACKGROUND: LPS-responsive beige-like anchor (LRBA) deficiency presents with susceptibility to infections, autoimmunity, and lymphoproliferation. The long-term efficacy of cytotoxic T-lymphocyte-associated antigen 4-immunoglobulin (abatacept) as targeted therapy for its immune dysregulatory features remains to be established. OBJECTIVE: To determine the clinical and immunologic features of LRBA deficiency and long-term efficacy of abatacept treatment in controlling the different disease manifestations. METHODS: Twenty-two LRBA-deficient patients were recruited from different immunology centers and followed prospectively. Eighteen patients on abatacept were evaluated every 3 months for long-term clinical and immunologic responses. LRBA expression, lymphocyte subpopulations, and circulating T follicular helper cells were determined by flow cytometry. RESULTS: The mean age of the patients was 13.4 +/- 7.9 years, and the follow-up period was 3.4 +/- 2.3 years. Recurrent infections (n = 19 [86.4%]), immune dysregulation (n = 18 [81.8%]), and lymphoproliferation (n = 16 [72.7%]) were common clinical features. The long-term benefits of abatacept in 16 patients were demonstrated by complete control of lymphoproliferation and chronic diarrhea followed by immune dysregulation, most notably autoimmune cytopenias. Weekly or every other week administration of abatacept gave better disease control compared with every 4 weeks. There were no serious side effects related to the abatacept therapy. Circulating T follicular helper cell frequencies were found to be a reliable biomarker of disease activity, which decreased on abatacept therapy in most subjects. However, high circulating T follicular helper cell frequencies persisted in 2 patients who had a more severe disease phenotype that was relatively resistant to abatacept therapy. CONCLUSIONS: Long-term abatacept therapy is effective in most patients with LRBA deficiency.eninfo:eu-repo/semantics/openAccessImmune dysregulatıonCtla-4 checpointMutationsPolyendocrinopathyEnteropathyDiseaseLps-responsive beige-like anchorImmune dysregulationAbataceptT follicular helper cellsAutoimmunityAbataceptAdaptor proteins, signal transducingAdolescentAdultChildChild preschoolFemaleHumansImmunologic deficiency syndromesImmunosuppressive agentsMaleMolecular targeted therapyTreatment outcomeYoung adultArticle0004957461000382-s2.0-85068767793279028007831238161AllergyImmunologyCommon Variable Immunodeficiency; Immunoglobulin Deficiency; ImmunosuppressionAbataceptBiological markerCarrier proteins and binding proteinsLipopolysaccharide responsive beige like anchor proteinUnclassified drugAbataceptImmunosuppressive agentLrba proteinHumanSignal transducing adaptor proteinAdolescentAdultArticleAutoimmunityChildChronic diarrheaClinical articleClinical featureControlled studyCytopeniaCytotoxicityDisease activityDisease severityDrug efficacyDrug responseFemaleFlow cytometryFollow upImmune dysregulationImmune responseImmunopathologyInfection sensitivityLong term careLymphocyte proliferationLymphocyte subpopulationMaleMolecularly targeted therapyPhenotypePreschool childProtein deficiencyProtein expressionRecurrent infectionSchool childT lymphocyteTfh cellTherapy effectYoung adultControlled clinical trialGeneticsImmune deficiencyMolecularly targeted therapyTreatment outcome