{"id":19767,"date":"2024-11-23T12:00:00","date_gmt":"2024-11-23T11:00:00","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2024\/11\/23\/a-novel-heterozygous-nfkb2-variant-in-a-multiplex-family-with-common-variable-immune-deficiency-and-autoantibodies-against-type-i-ifns\/"},"modified":"2024-11-23T12:00:00","modified_gmt":"2024-11-23T11:00:00","slug":"a-novel-heterozygous-nfkb2-variant-in-a-multiplex-family-with-common-variable-immune-deficiency-and-autoantibodies-against-type-i-ifns","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2024\/11\/23\/a-novel-heterozygous-nfkb2-variant-in-a-multiplex-family-with-common-variable-immune-deficiency-and-autoantibodies-against-type-i-ifns\/","title":{"rendered":"A Novel Heterozygous NFKB2 Variant in a Multiplex Family with Common Variable Immune Deficiency and Autoantibodies Against Type I IFNs"},"content":{"rendered":"<div>\n<p>J Clin Immunol. 2024 Nov 23;45(1):48. doi: 10.1007\/s10875-024-01843-1.<\/p>\n<p>ABSTRACT<\/p>\n<p>We studied a family with three male individuals across two generations affected by common variable immune deficiency (CVID). We identified a novel missense heterozygous variant (c.2602T&gt;A:p.Y868N) of NFKB2 in all patients and not in healthy relatives. Functional studies of the mutant allele in an overexpression system and of the patients&#8217; cells confirmed the deleteriousness of the NFKB2 variant and genotype, respectively, on the activation of the non-canonical NF-\u03baB signaling pathway. Impaired processing of p100 into p52 underlies p100 accumulation, which results in gain-of-function (GOF) of I\u03baB\u03b4 inhibitory activity and loss-of-function (LOF) of p52 transcriptional activity. The three patients&#8217; plasma contained autoantibodies that neutralized IFN-\u03b12 and\/or IFN-\u03c9, accounting for the severe or recurrent viral diseases of the patients, including influenza pneumonia in one sibling, and severe COVID-19 and recurrent herpes labialis in another. Our results confirm that NFKB2 alleles that are I\u03baB\u03b4 GOF and p52 LOF can underlie CVID and drive the production of autoantibodies neutralizing type I IFNs, thereby predisposing to severe viral diseases.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39579251\/?utm_source=WordPress&amp;utm_medium=rss&amp;utm_campaign=journals&amp;utm_content=8102137&amp;ff=20241124004707&amp;v=2.18.0.post9+e462414\">39579251<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1007\/s10875-024-01843-1\">10.1007\/s10875-024-01843-1<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Clin Immunol. 2024 Nov 23;45(1):48. doi: 10.1007\/s10875-024-01843-1. ABSTRACT We studied a family with three male individuals across two generations affected by common variable immune deficiency (CVID). We identified a novel missense heterozygous variant (c.2602T&gt;A:p.Y868N) of NFKB2 in all patients and not in healthy relatives. Functional studies of the mutant allele in an overexpression system &#8230; <a title=\"A Novel Heterozygous NFKB2 Variant in a Multiplex Family with Common Variable Immune Deficiency and Autoantibodies Against Type I IFNs\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2024\/11\/23\/a-novel-heterozygous-nfkb2-variant-in-a-multiplex-family-with-common-variable-immune-deficiency-and-autoantibodies-against-type-i-ifns\/\" aria-label=\"Read more about A Novel Heterozygous NFKB2 Variant in a Multiplex Family with Common Variable Immune Deficiency and Autoantibodies Against Type I IFNs\">Read more<\/a><\/p>\n","protected":false},"author":0,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[69,42],"tags":[],"class_list":["post-19767","post","type-post","status-publish","format-standard","hentry","category-journal-of-clinical-immunology","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/19767","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=19767"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/19767\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=19767"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=19767"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=19767"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}