{"id":44346,"date":"2025-09-30T12:00:00","date_gmt":"2025-09-30T10:00:00","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/09\/30\/a-novel-cause-of-cidp-homozygous-hotspot-mutation-c-793-c-t-in-casp8-gene\/"},"modified":"2025-09-30T12:00:00","modified_gmt":"2025-09-30T10:00:00","slug":"a-novel-cause-of-cidp-homozygous-hotspot-mutation-c-793-c-t-in-casp8-gene","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/09\/30\/a-novel-cause-of-cidp-homozygous-hotspot-mutation-c-793-c-t-in-casp8-gene\/","title":{"rendered":"A Novel Cause of CIDP: Homozygous Hotspot Mutation, c.793\u00a0C\u2009>\u2009T in CASP8 Gene"},"content":{"rendered":"
\n

J Clin Immunol<\/b>. 2025 Sep 30;45(1):130. doi: 10.1007\/s10875-025-01931-w.<\/p>\n

ABSTRACT<\/b><\/p>\n

BACKGROUND: Caspase-8 enzyme deficiency (CED) is a rare autosomal recessive inborn error of immunity with autoimmune lymphoproliferative syndromes (ALPS), deficient extrinsic apoptosis and hyperactivation of the mammalian target of rapamycin (mTOR) pathway.<\/p>\n

METHODS: Features of our patient with early onset chronic inflammatory demyelinating polyneuropathy (CIDP) are presented in detail. We report features of ALPS due to CED (ALPS-CED) in 6 patients in previous literature and our patient with the homozygous hotspot mutation, c.793 C > T in the CASP8 gene, and demonstrate that such mutation is a novel cause of CIDP.<\/p>\n

RESULTS: Our patient fits the spectrum of genetic disorders causing ALPS with dysregulation of the mTOR pathway. Autoimmune lymphoproliferative syndrome with FAS mutations (ALPS-FAS) is also associated with hyperactivation of the mTOR pathway but hematologic symptoms are more severe than ALPS-CED. Both ALPS-FAS and ALPS-CED lead to autoimmunity and improve with use of mTOR inhibitors. ALPS-FAS is characterized by the elevation of alpha beta-double negative T-cells (DNT) and hypergammaglobulinemia, while such features are not prominent in ALPS-CED. Patients with ALPS-CED not only suffer from ALPS but also present with an immune deficiency and a chronic inflammatory state both related to non-apoptotic functions of caspase-8.<\/p>\n

CONCLUSIONS: Both ALPS-FAS and ALPS-CED are characterized by deficient extrinsic apoptosis and dysregulation of the mTOR pathway. Compared to ALPS-FAS, the phenotype of ALPS-CED is more complex due to a more diffuse dysfunction of the non-apoptotic pathways. To our knowledge, early onset CIDP in a patient with homozygous hotspot mutation, c.793 C > T in CASP8, has not been reported previously.<\/p>\n

PMID:41026346<\/a> | DOI:10.1007\/s10875-025-01931-w<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"

J Clin Immunol. 2025 Sep 30;45(1):130. doi: 10.1007\/s10875-025-01931-w. ABSTRACT BACKGROUND: Caspase-8 enzyme deficiency (CED) is a rare autosomal recessive inborn error of immunity with autoimmune lymphoproliferative syndromes (ALPS), deficient extrinsic apoptosis and hyperactivation of the mammalian target of rapamycin (mTOR) pathway. METHODS: Features of our patient with early onset chronic inflammatory demyelinating polyneuropathy (CIDP) are … Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[69,42],"tags":[],"class_list":["post-44346","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\/44346","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"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=44346"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/44346\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=44346"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=44346"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=44346"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}