Long-term outcome of LRBA deficiency in 76 patients after various treatment modalities as evaluated by the immune deficiency and dysregulation activity (IDDA) score

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dc.contributor.authorTesch, Victoria Katharina
dc.contributor.authorAbolhassani, Hassan
dc.contributor.authorShadur, Bella
dc.contributor.authorZobel, Joachim
dc.contributor.authorMareika, Yuliya
dc.contributor.authorSharapova, Svetlana
dc.contributor.authorKarakoc-Aydiner, Elif
dc.date.accessioned2024-02-23T14:12:30Z
dc.date.available2024-02-23T14:12:30Z
dc.date.issued2020
dc.departmentNEÜen_US
dc.description.abstractBackground: Recent findings strongly support hematopoietic stem cell transplantation (HSCT) in patients with severe presentation of LPS-responsive beige-like anchor protein (LRBA) deficiency, but long-term follow-up and survival data beyond previous patient reports or meta-reviews are scarce for those patients who do not receive a transplant. Objective: This international retrospective study was conducted to elucidate the longitudinal clinical course of patients with LRBA deficiency who do and do not receive a transplant. Method: We assessed disease burden and treatment responses with a specially developed immune deficiency and dysregulation activity score, reflecting the sum and severity of organ involvement and infections, days of hospitalization, supportive care requirements, and performance indices. Results: Of 76 patients with LRBA deficiency from 29 centers (median follow-up, 10 years; range, 1-52), 24 underwent HSCT from 2005 to 2019. The overall survival rate after HSCT (median follow-up, 20 months) was 70.8% (17 of 24 patients); all deaths were due to nonspecific, early, transplant-related mortality. Currently, 82.7% of patients who did not receive a transplant (43 of 52; age range, 3-69 years) are alive. Of 17 HSCT survivors, 7 are in complete remission and 5 are in good partial remission without treatment (together, 12 of 17 [70.6%]). In contrast, only 5 of 43 patients who did not receive a transplant (11.6%) are without immunosuppression. Immune deficiency and dysregulation activity scores were significantly lower in patients who survived HSCT than in those receiving conventional treatment (P = .005) or in patients who received abatacept or sirolimus as compared with other therapies, and in patients with residual LRBA expression. Higher disease burden, longer duration before HSCT, and lung involvement were associated with poor outcome. Conclusion: The lifelong disease activity, implying a need for immunosuppression and risk of malignancy, must be weighed against the risks of HSCT.en_US
dc.description.sponsorshipStyrian Children's Cancer Aid Foundation; Slovenian Research Agency [P3-0343]; Jonas S_oderquist Foundation; Scientific and Technological Research Council of Turkey [217S847, 318S202]; Deutsche Forschungsgemeinschaft under Germany's Excellence Strategy [390939984, 39087428]; E-Rare program of the European Union by the Deutsche Forschungsgemeinschaft [GR1617/14-1/iPAD]; Netzwerke Seltener Erkrankungen of the German Ministry of Education and Research [GAIN_ 01GM1910A]; Finnish Foundation for Pediatric Research and Pediatric Research Center, HUS Helsinki University Hospital; Graduate Research Training Scholarship of the Australian government; Hadassah Australia; ERN-RITA network [739543]en_US
dc.description.sponsorshipM.G. Seidel and the Research Unit for Pediatric Hematology and Immunology are supported in part by the Styrian Children's Cancer Aid Foundation. M. Avbeli Stefanija was supported by the Slovenian Research Agency (grant P3-0343). H. Abolhassani was supported by the Jonas S_oderquist Foundation. S. Baris was supported by the Scientific and Technological Research Council of Turkey for the diagnosis of patients with LRBA deficiency (grants 217S847 and 318S202). B. Grimbacher receives support through the Deutsche Forschungsgemeinschaft under Germany's Excellence Strategy (CIBSS-EXC-2189-Project ID 390939984 and RESIST-EXC 2155-Project ID 39087428); through the E-Rare program of the European Union, managed by the Deutsche Forschungsgemeinschaft (grant GR1617/14-1/iPAD); and through the Netzwerke Seltener Erkrankungen of the German Ministry of Education and Research (grant GAIN_ 01GM1910A). M.R.J. Sepp_anen was supported by the Finnish Foundation for Pediatric Research and Pediatric Research Center, HUS Helsinki University Hospital. I. Meyts is a member of the ERN-RITA network (project identification number 739543). B. Shadur is supported by a Graduate Research Training Scholarship of the Australian government and by Hadassah Australia.en_US
dc.identifier.doi10.1016/j.jaci.2019.12.896
dc.identifier.endpage1463en_US
dc.identifier.issn0091-6749
dc.identifier.issn1097-6825
dc.identifier.issue5en_US
dc.identifier.pmid31887391en_US
dc.identifier.scopus2-s2.0-85078904882en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage1452en_US
dc.identifier.urihttps://doi.org/10.1016/j.jaci.2019.12.896
dc.identifier.urihttps://hdl.handle.net/20.500.12452/12085
dc.identifier.volume145en_US
dc.identifier.wosWOS:000531063400017en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherMosby-Elsevieren_US
dc.relation.ispartofJournal Of Allergy And Clinical Immunologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectInborn Error Of Immunityen_US
dc.subjectPrimary Immunodeficiency Disorderen_US
dc.subjectImmune Dysregulationen_US
dc.subjectClinical Scoreen_US
dc.subjectPerformance Scaleen_US
dc.subjectHematopoietic Stem Cell Transplantationen_US
dc.subjectCtla4en_US
dc.subjectAbatacepten_US
dc.subjectSirolimusen_US
dc.subjectCombined Immunodeficiencyen_US
dc.titleLong-term outcome of LRBA deficiency in 76 patients after various treatment modalities as evaluated by the immune deficiency and dysregulation activity (IDDA) scoreen_US
dc.typeArticleen_US

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