Clinical heterogeneity in families with multiple cases of inborn errors of immunity

Bibliographische Detailangaben
Veröffentlicht in:	Clinical immunology (Orlando, Fla.). - 1999. - 259(2024) vom: 10. Feb., Seite 109896
1. Verfasser:	Delavari, Samaneh (VerfasserIn)
Weitere Verfasser:	Rasouli, Seyed Erfan, Fekrvand, Saba, Chavoshzade, Zahra, Mahdaviani, Seyed Alireza, Shirmast, Paniz, Sharafian, Samin, Sherkat, Roya, Momen, Tooba, Aleyasin, Soheila, Ahanchian, Hamid, Sadeghi-Shabestari, Mahnaz, Esmaeilzadeh, Hossein, Barzamini, Sahar, Tarighatmonfared, Fateme, Salehi, Helia, Esmaeili, Marzie, Marzani, Zahra, Fathi, Nazanin, Abolnezhadian, Farhad, Rad, Mina Kianmanesh, Saeedi-Boroujeni, Ali, Shirkani, Afshin, Bagheri, Zahra, Salami, Fereshte, Shad, Tannaz Moeini, Marzbali, Mahsa Yousefpour, Mojtahedi, Hanieh, Razavi, Azadehsadat, Tavakolinia, Naeimeh, Cheraghi, Taher, Tavakol, Marzieh, Shafiei, Alireza, Behniafard, Nasrin, Ebrahimi, Sare Sadat, Sepahi, Najmeh, Ghaneimoghadam, Amirhossein, Rezaei, Arezou, Kalantari, Arash, Abolhassani, Hassan, Rezaei, Nima
Format:	Online-Aufsatz
Sprache:	English
Veröffentlicht:	2024
Zugriff auf das übergeordnete Werk:	Clinical immunology (Orlando, Fla.)
Schlagworte:	Journal Article Research Support, Non-U.S. Gov't Congenital inheritance Inborn errors of immunity Multiple cases Penetrance Primary immunodeficiency Adaptor Proteins, Signal Transducing Antigens, CD19 STK4 protein, human mehr... EC 2.7.1.11 Protein Serine-Threonine Kinases EC 2.7.11.1 Intracellular Signaling Peptides and Proteins

Beschreibung
Zusammenfassung:	Copyright © 2024 Elsevier Inc. All rights reserved. BACKGROUND: Inborn errors of immunity (IEI) are a diverse range of genetic immune system illnesses affecting the innate and/or adaptive immune systems. Variable expressivity and incomplete penetrance have been reported in IEI patients with similar clinical diagnoses or even the same genetic mutation METHODS: Among all recorded patients in the national IEI registry, 193 families with multiple cases have been recognized. Clinical, laboratory and genetic variability were compared between 451 patients with different IEI entities RESULTS: The diagnosis of the first children led to the earlier diagnosis, lower diagnostic delay, timely treatment and improved survival in the second children in the majority of IEI. The highest discordance in familial lymphoproliferation, autoimmunity and malignancy were respectively observed in STK4 deficiency, DNMT3B deficiency and ATM deficiency. Regarding immunological heterogeneity within a unique family with multiple cases of IEI, the highest discordance in CD3+, CD4+, CD19+, IgM and IgA levels was observed in syndromic combined immunodeficiencies (CID), while non-syndromic CID particularly severe combined immunodeficiency (SCID) manifested the highest discordance in IgG levels. Identification of the first ATM-deficient patient can lead to improved care and better survival in the next IEI children from the same family CONCLUSION: Intrafamilial heterogeneity in immunological and/or clinical features could be observed in families with multiple cases of IEI indicating the indisputable role of appropriate treatment and preventive environmental factors besides specific gene mutations in the variable observed penetrance or expressivity of the disease. This also emphasizes the importance of implementing genetic evaluation in all members of a family with a history of IEI even if there is no suspicion of an underlying IEI as other factors besides the underlying genetic defects might cause a milder phenotype or delay in presentation of clinical features. Thus, affected patients could be timely diagnosed and treated, and their quality of life and survival would improve
Beschreibung:	Date Completed 29.01.2024 Date Revised 10.04.2024 published: Print-Electronic Citation Status MEDLINE
ISSN:	1521-7035
DOI:	10.1016/j.clim.2024.109896