Abatacept as a Long-Term Targeted Therapy for LRBA Deficiency

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dc.contributor.authorKiykim, Ayca
dc.contributor.authorOgulur, Ismail
dc.contributor.authorDursun, Esra
dc.contributor.authorCharbonnier, Louis Marie
dc.contributor.authorNain, Ercan
dc.contributor.authorCekic, Sukru
dc.contributor.authorDogruel, Dilek
dc.date.accessioned2024-02-23T14:12:31Z
dc.date.available2024-02-23T14:12:31Z
dc.date.issued2019
dc.departmentNEÜen_US
dc.description.abstractBACKGROUND: 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. (C) 2019 American Academy of Allergy, Asthma & Immunologyen_US
dc.description.sponsorshipScientific and Technological Research Council of Turkey [217S847]; National Institutes of Health [5R01AI085090]en_US
dc.description.sponsorshipThis work was supported by grants from the Scientific and Technological Research Council of Turkey (grant no. 217S847 to S.B.) and the National Institutes of Health (grant no. 5R01AI085090 to T.A.C.).en_US
dc.identifier.doi10.1016/j.jaip.2019.06.011
dc.identifier.endpage+en_US
dc.identifier.issn2213-2198
dc.identifier.issn2213-2201
dc.identifier.issue8en_US
dc.identifier.pmid31238161en_US
dc.identifier.scopus2-s2.0-85068767793en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage2790en_US
dc.identifier.urihttps://doi.org/10.1016/j.jaip.2019.06.011
dc.identifier.urihttps://hdl.handle.net/20.500.12452/12093
dc.identifier.volume7en_US
dc.identifier.wosWOS:000495746100038en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relation.ispartofJournal Of Allergy And Clinical Immunology-In Practiceen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectLps-Responsive Beige-Like Anchoren_US
dc.subjectImmune Dysregulationen_US
dc.subjectAbatacepten_US
dc.subjectT Follicular Helper Cellsen_US
dc.subjectAutoimmunityen_US
dc.titleAbatacept as a Long-Term Targeted Therapy for LRBA Deficiencyen_US
dc.typeArticleen_US

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