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

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dc.contributor.authorBARIŞ, SAFA
dc.contributor.authorAYDINER, ELİF
dc.contributor.authorÖZEN, AHMET OĞUZHAN
dc.contributor.authorsCatak M. C., Akcam B., Bilgic Eltan S., Babayeva R., Karakus I. S., Akgun G., Baser D., Bulutoglu A., Bayram F., Kasap N., et al.
dc.date.accessioned2023-05-08T08:07:17Z
dc.date.available2023-05-08T08:07:17Z
dc.date.issued2022-10-01
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.
dc.identifier.citationCatak M. C., Akcam B., Bilgic Eltan S., Babayeva R., Karakus I. S., Akgun G., Baser D., Bulutoglu A., Bayram F., Kasap N., et al., "Comparing the levels of CTLA-4-dependent biological defects in patients with LRBA deficiency and CTLA-4 insufficiency", ALLERGY, cilt.77, sa.10, ss.3108-3123, 2022
dc.identifier.doi10.1111/all.15331
dc.identifier.endpage3123
dc.identifier.issn0105-4538
dc.identifier.issue10
dc.identifier.startpage3108
dc.identifier.urihttps://onlinelibrary.wiley.com/doi/epdf/10.1111/all.15331
dc.identifier.urihttps://hdl.handle.net/11424/289151
dc.identifier.volume77
dc.language.isoeng
dc.relation.ispartofALLERGY
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectTıp
dc.subjectYaşam Bilimleri
dc.subjectSağlık Bilimleri
dc.subjectTemel Bilimler
dc.subjectMedicine
dc.subjectLife Sciences
dc.subjectHealth Sciences
dc.subjectNatural Sciences
dc.subjectALERJİ
dc.subjectKlinik Tıp
dc.subjectKlinik Tıp (MED)
dc.subjectİmmünoloji
dc.subjectYaşam Bilimleri (LIFE)
dc.subjectALLERGY
dc.subjectCLINICAL MEDICINE
dc.subjectClinical Medicine (MED)
dc.subjectIMMUNOLOGY
dc.subjectLife Sciences (LIFE)
dc.subjectİmmünoloji ve Alerji
dc.subjectGenel İmmünoloji ve Mikrobiyoloji
dc.subjectImmunology and Allergy
dc.subjectImmunology
dc.subjectGeneral Immunology and Microbiology
dc.subjectCTLA-4
dc.subjectinborn errors of immunity
dc.subjectLRBA
dc.subjectT follicular helper cells
dc.subjectTreg
dc.subjectREGULATORY T-CELLS
dc.subjectIMMUNE DYSREGULATION
dc.subjectMUTATIONS
dc.subjectDISEASE
dc.subjectDEMETHYLATION
dc.subjectENDOCYTOSIS
dc.subjectPHENOTYPES
dc.subjectFAMILY
dc.subjectGENE
dc.subjectCTLA- 4
dc.subjectinborn errors of immunity
dc.subjectLRBA
dc.subjectT follicular helper cells
dc.subjectTreg
dc.titleComparing the levels of CTLA-4-dependent biological defects in patients with LRBA deficiency and CTLA-4 insufficiency
dc.typearticle
dspace.entity.typePublication
local.avesis.idfaebc424-5359-4cbc-8d3c-fd2b17289831
local.indexed.atWOS
local.indexed.atPUBMED
local.indexed.atSCOPUS
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relation.isAuthorOfPublication.latestForDiscovery5b392475-f11d-44b3-b251-4fe8e6b7dbb9

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