Comparing the levels of CTLA-4-dependent biological defects in patients with LRBA deficiency and CTLA-4 insufficiency

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dc.contributor.authorCatak, Mehmet C.
dc.contributor.authorAkcam, Bengu
dc.contributor.authorEltan, Sevgi Bilgic
dc.contributor.authorBabayeva, Royala
dc.contributor.authorKarakus, Ibrahim S.
dc.contributor.authorAkgun, Gamze
dc.contributor.authorBaser, Dilek
dc.date.accessioned2024-02-23T14:24:01Z
dc.date.available2024-02-23T14:24:01Z
dc.date.issued2022
dc.departmentNEÜen_US
dc.description.abstractBackground Lipopolysaccharide-responsive beige-like anchor protein (LRBA) deficiency and cytotoxic T-lymphocyte protein-4 (CTLA-4) insufficiency are recently described disorders that present with susceptibility to infections, autoimmunity, and lymphoproliferation. Clinical and immunological comparisons of the diseases with long-term follow-up have not been previously reported. We sought to compare the clinical and laboratory manifestations of both diseases and investigate the role of flow cytometry in predicting the genetic defect in patients with LRBA deficiency and CTLA-4 insufficiency. Methods Patients were evaluated clinically with laboratory assessments for lymphocyte subsets, T follicular helper cells (T-FH), LRBA expression, and expression of CD25, FOXP3, and CTLA4 in regulatory T cells (Tregs) at baseline and 16 h post-stimulation. Results LRBA-deficient patients (n = 29) showed significantly early age of symptom onset, higher rates of pneumonia, autoimmunity, chronic diarrhea, and failure to thrive compared to CTLA-4 insufficiency (n = 12). In total, 29 patients received abatacept with favorable responses and the overall survival probability was not different between transplanted versus non-transplanted patients in LRBA deficiency. Meanwhile, higher probability of survival was observed in CTLA-4-insufficient patients (p = 0.04). The T-cell subsets showed more deviation to memory cells in CTLA-4-insufficiency, accompanied by low percentages of Treg and dysregulated cT(FH) cells response in both diseases. Cumulative numbers of autoimmunities positively correlated with cT(FH) frequencies. Baseline CTLA-4 expression was significantly diminished in LRBA deficiency and CTLA-4 insufficiency, but significant induction in CTLA-4 was observed after short-term T-cell stimulation in LRBA deficiency and controls, while this elevation was less in CTLA-4 insufficiency, allowing to differentiate this disease from LRBA deficiency with high sensitivity (87.5%) and specificity (90%). Conclusion This cohort provided detailed clinical and laboratory comparisons for LRBA deficiency and CTLA-4 insufficiency. The flow cytometric approach is useful in predicting the defective gene; thus, targeted sequencing can be conducted to provide rapid diagnosis and treatment for these diseases impacting the CTLA-4 pathway.en_US
dc.identifier.doi10.1111/all.15331
dc.identifier.endpage3123en_US
dc.identifier.issn0105-4538
dc.identifier.issn1398-9995
dc.identifier.issue10en_US
dc.identifier.pmid35491430en_US
dc.identifier.scopus2-s2.0-85129823979en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage3108en_US
dc.identifier.urihttps://doi.org/10.1111/all.15331
dc.identifier.urihttps://hdl.handle.net/20.500.12452/13778
dc.identifier.volume77en_US
dc.identifier.wosWOS:000793928900001en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relation.ispartofAllergyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectCtla-4en_US
dc.subjectInborn Errors Of Immunityen_US
dc.subjectLrbaen_US
dc.subjectT Follicular Helper Cellsen_US
dc.subjectTregen_US
dc.titleComparing the levels of CTLA-4-dependent biological defects in patients with LRBA deficiency and CTLA-4 insufficiencyen_US
dc.typeArticleen_US

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