Genomic spectrum and phenotypic heterogeneity of human IL-21 receptor deficiency

Basit Öğe Kaydı
dc.authoridGülsün Tezcan Karasu / 0000-0001-5700-5919
dc.authorscopusidGülsün Tezcan Karasu / 56382958800
dc.authorwosidGülsün Tezcan Karasu / IAF-9902-2023
dc.contributor.authorÇağdaş, Deniz
dc.contributor.authorBarış, Safa
dc.contributor.authorWorley, Lisa
dc.contributor.authorLangley, David B.
dc.contributor.authorMetin, Ayşe
dc.contributor.authorTezcan Karasu, Gülsün
dc.date.accessioned2021-05-04T08:32:17Z
dc.date.available2021-05-04T08:32:17Z
dc.date.issued2021en_US
dc.departmentİstinye Üniversitesi, Tıp Fakültesi, Dahili Tıp Bilimleri Bölümüen_US
dc.description.abstractBiallelic inactivating mutations in IL21R causes a combined immunodeficiency that is often complicated by cryptosporidium infections. While eight IL-21R-deficient patients have been reported previously, the natural course, immune characteristics of disease, and response to hematopoietic stem cell transplantation (HSCT) remain to be comprehensively examined. In our study, we have collected clinical histories of 13 patients with IL-21R deficiency from eight families across seven centers worldwide, including five novel patients identified by exome or NGS panel sequencing. Eight unique mutations in IL21R were identified in these patients, including two novel mutations. Median age at disease onset was 2.5 years (0.5-7 years). The main clinical manifestations were recurrent bacterial (84.6%), fungal (46.2%), and viral (38.5%) infections; cryptosporidiosis-associated cholangitis (46.2%); and asthma (23.1%). Inflammatory skin diseases (15.3%) and recurrent anaphylaxis (7.9%) constitute novel phenotypes of this combined immunodeficiency. Most patients exhibited hypogammaglobulinemia and reduced proportions of memory B cells, circulating T follicular helper cells, MAIT cells and terminally differentiated NK cells. However, IgE levels were elevated in 50% of IL-21R-deficient patients. Overall survival following HSCT (6 patients, mean follow-up 1.8 year) was 33.3%, with pre-existing organ damage constituting a negative prognostic factor. Mortality of non-transplanted patients (n = 7) was 57.1%. Our detailed analysis of the largest cohort of IL-21R-deficient patients to date provides in-depth clinical, immunological and immunophenotypic features of these patients, thereby establishing critical non-redundant functions of IL-21/IL-21R signaling in lymphocyte differentiation, humoral immunity and host defense against infection, and mechanisms of disease pathogenesis due to IL-21R deficiency. Outcome following HSCT depends on prior chronic infections and organ damage, which should thus be considered as early as possible following molecular diagnosis.en_US
dc.identifier.citationCagdas, D., Mayr, D., Baris, S. et al. Genomic Spectrum and Phenotypic Heterogeneity of Human IL-21 Receptor Deficiency. J Clin Immunol (2021). https://doi.org/10.1007/s10875-021-01031-5en_US
dc.identifier.doi10.1007/s10875-021-01031-5en_US
dc.identifier.pmid33929673en_US
dc.identifier.scopus2-s2.0-85105382665en_US
dc.identifier.scopusqualityN/Aen_US
dc.identifier.urihttps://doi.org/10.1007/s10875-021-01031-5
dc.identifier.urihttps://hdl.handle.net/20.500.12713/1715
dc.identifier.wosWOS:000645896900001en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.institutionauthorTezcan Karasu, Gülsün
dc.language.isoenen_US
dc.publisherSpringeren_US
dc.relation.ispartofJournal of Clinical Immunologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectB Cell Differentiationen_US
dc.subjectIL-21/IL-21R Signalingen_US
dc.subjectSTAT3en_US
dc.subjectT Follicular Helper Cellsen_US
dc.titleGenomic spectrum and phenotypic heterogeneity of human IL-21 receptor deficiencyen_US
dc.typeArticleen_US

Dosyalar

Orijinal paket
Listeleniyor 1 - 1 / 1
Küçük Resim Yok
İsim:
53.pdf
Boyut:
1.39 MB
Biçim:
Adobe Portable Document Format
Açıklama:
Tam Metin / Full Text
İndir
Lisans paketi
Listeleniyor 1 - 1 / 1
Küçük Resim Yok
İsim:
license.txt
Boyut:
1.44 KB
Biçim:
Item-specific license agreed upon to submission
Açıklama:
İndir

Koleksiyon

PubMed İndeksli Yayınlar Koleksiyonu
Dahili Tıp Bilimleri Bölümü Makale Koleksiyonu
Scopus İndeksli Yayınlar Koleksiyonu
WoS İndeksli Yayınlar Koleksiyonu