Long-term follow up of families with pathogenic <em>NFKB1</em> variants reveals incomplete penetrance and frequent inflammatory sequelae

Tuovinen, Elina A.; Kuismin, Outi; Soikkonen, Leila; Martelius, Timi; Kaustio, Meri; Hämäläinen, Sari; Viskari, Hanna; Syrjänen, Jaana; Wartiovaara-Kautto, Ulla; Eklund, Kari K.; Saarela, Janna; Varjosalo, Markku; Kere, Juha; Hautala, Timo; Seppänen, Mikko R. J.

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	Tuovinen, E. A., Kuismin, O., Soikkonen, L., Martelius, T., Kaustio, M., Hämäläinen, S., Viskari, H., Syrjänen, J., Wartiovaara-Kautto, U., Eklund, K. K., Saarela, J., Varjosalo, M., Kere, J., Hautala, T., & Seppänen, M. R. J. (2023). Long-term follow up of families with pathogenic NFKB1 variants reveals incomplete penetrance and frequent inflammatory sequelae. In Clinical Immunology (Vol. 246, p. 109181). Elsevier BV. https://doi.org/10.1016/j.clim.2022.109181 Long-term follow up of families with pathogenic NFKB1 variants reveals incomplete penetrance and frequent inflammatory sequelae Saved in:
Author:	Tuovinen, Elina A.^1,2,3; Kuismin, Outi^4,5; Soikkonen, Leila^4,5; Martelius, Timi⁶; Kaustio, Meri⁷; Hämäläinen, Sari⁸; Viskari, Hanna^9,10; Syrjänen, Jaana^9,10; Wartiovaara-Kautto, Ulla^11,12; Eklund, Kari K.^13,14; Saarela, Janna^7,15; Varjosalo, Markku¹⁶; Kere, Juha^2,17,18; Hautala, Timo^19,20; Seppänen, Mikko R. J.^1,3,21
Organizations:	¹Translational Immunology Research Program, University of Helsinki, Helsinki, Finland ²Folkhälsan Research Center, Helsinki, Finland ³Pediatric Research Center, New Children's Hospital, University of Helsinki and HUS Helsinki University Hospital, Helsinki, Finland ⁴PEDEGO Research Unit, University of Oulu, Oulu, Finland ⁵Department of Clinical Genetics and Medical Research Center, Oulu University Hospital, Oulu, Finland ⁶Inflammation Center, Department of Infectious Disease, Helsinki University Hospital, Helsinki, Finland ⁷Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland ⁸Department of Medicine, Institute of Clinical Medicine/ Internal Medicine, Kuopio University Hospital, Kuopio, Finland ⁹Department of Internal Medicine, Tampere University Hospital, Tampere, Finland ¹⁰Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland ¹¹Department of Hematology, Helsinki University Hospital Comprehensive Cancer Center, University of Helsinki, Helsinki, Finland ¹²Applied Tumor Genomics Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland ¹³Department of Rheumatology, Inflammation Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland ¹⁴Orton Orthopedic Hospital, Helsinki, Finland ¹⁵Centre for Molecular Medicine Norway, University of Oslo, Oslo, Norway ¹⁶Systems Biology Research Group and Proteomics Unit, Institute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, Finland ¹⁷Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden ¹⁸Stem Cells and Metabolism Research Program, University of Helsinki, Helsinki, Finland ¹⁹Research Unit of Biomedicine, University of Oulu, Oulu, Finland ²⁰Department of Internal Medicine, Oulu University Hospital, Oulu, Finland ²¹Rare Diseases Center and Pediatric Research Center, New Children's Hospital, University of Helsinki and HUS Helsinki University Hospital, Helsinki, Finland
Format:	article
Version:	published version
Access:	open
Online Access:	PDF Full Text (PDF, 0.5 MB)
Persistent link:	http://urn.fi/urn:nbn:fi-fe20231002138131
Language:	English
Published:	Elsevier, 2022
Publish Date:	2023-10-02
Description:	Abstract Nuclear factor κ light-chain enhancer of activated B cells (NF-κB) family of evolutionarily conserved transcription factors are involved in key cellular signaling pathways. Previously, hypogammaglobulinemia and common variable immunodeficiency (CVID)-like phenotypes have been associated with NFKB1 variants and loss-of-function NFKB1 variants have been reported as the most common monogenic cause for CVID among Europeans. Here, we describe a Finnish cohort of NFKB1 carriers consisting of 31 living subjects in six different families carrying five distinct heterozygous variants. In contrast to previous reports, the clinical penetrance was not complete even with advancing age and the prevalence of CVID/hypogammaglobulinemia was significantly lower, whereas (auto)inflammatory manifestations were more common (42% of the total cohort). At current stage of knowledge, routine genetic screening of asymptomatic individuals is not recommended, but counseling of potential adult carriers seems necessary. see all 
Series:	Clinical immunology
ISSN:	1521-6616
ISSN-E:	1521-7035
ISSN-L:	1521-6616
Volume:	246
Article number:	109181
DOI:	10.1016/j.clim.2022.109181
OADOI:	https://oadoi.org/10.1016/j.clim.2022.109181
Type of Publication:	A1 Journal article – refereed
Field of Science:	3111 Biomedicine
Subjects:	Autoinflammation Common variable immunodeficiency Hypogammaglobulinemia Inborn errors of immunity NFKB1 Article
Funding:	Funding was received by Emil Aaltonen Foundation (ET), Bio- medicum Foundation (ET), The Finnish Medical Foundation (ET), Sanofi-Genzyme (JSa), Academy of Finland (MV), Sigrid Jus ́elius Foundation (JK), Oulu University Hospital VTR (TH), The Foundation for Pediatric Research (MS), HUS Pediatric Research Center and Helsinki University Hospital Research Funds (MS, KKE), Finska L ̈akares ̈allskapet (KKE) and the Erkko Foundation (KKE, MS).
Copyright information:	© 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
	https://creativecommons.org/licenses/by/4.0/

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Long-term follow up of families with pathogenic NFKB1 variants reveals incomplete penetrance and frequent inflammatory sequelae

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