{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:07:05Z","timestamp":1772118425152,"version":"3.50.1"},"reference-count":24,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:00:00Z","timestamp":1741737600000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Inborn deficiencies of the alternative pathway (AP) of the complement system have been associated with life\u2010threatening infections, mainly by encapsulated bacteria. Complete factor D (FD) deficiencies have been reported in only seven families in the literature. We report two new cases of biochemically and genetically confirmed complete FD deficiency, including the first in a Down syndrome patient. The index cases respectively suffered from severe\n                    <jats:italic>H. influenza<\/jats:italic>\n                    and\n                    <jats:italic>N. meningitidis<\/jats:italic>\n                    infections. Their FD activity was undetectable but was restored by adding recombinant human FD. FD levels were undetectable in the plasma of both patients using ELISA. Genetic analysis of the\n                    <jats:italic>CFD<\/jats:italic>\n                    gene identified a homozygous missense variant p.M40R in one patient, and compound heterozygous variants\u2014a nonsense mutation p.Cys148* and a splice site variant c.212+2T&gt;G\u2014in the other. Patients with Down syndrome are more susceptible to infections, but this case highlights the importance of investigating the complement system, particularly the AP, even in those with Down syndrome or other secondary immune deficiencies. A familial study should follow if a congenital deficiency is found. The natural history of patients with inherited complete FD deficiency underscores the necessity of preventive measures against encapsulated bacteria for those receiving therapeutic MASP\u20103 or FD inhibitors.\n                  <\/jats:p>","DOI":"10.1002\/eji.202451536","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T07:29:32Z","timestamp":1741764572000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Two New Kindreds with Complete Factor D Deficiency"],"prefix":"10.1002","volume":"55","author":[{"given":"Mathilde","family":"Puel","sequence":"first","affiliation":[{"name":"Department of Immunology Assistance Publique\u2010 H\u00f4pitaux de Paris (AP\u2010HP) Georges Pompidou European Hospital  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenza","family":"Rwayane","sequence":"additional","affiliation":[{"name":"Department of Immunology Assistance Publique\u2010 H\u00f4pitaux de Paris (AP\u2010HP) Georges Pompidou European Hospital  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula","family":"Vieira Martins","sequence":"additional","affiliation":[{"name":"Department of Immunology Assistance Publique\u2010 H\u00f4pitaux de Paris (AP\u2010HP) Georges Pompidou European Hospital  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marwa","family":"Chbihi","sequence":"additional","affiliation":[{"name":"Pediatric Immunology\u2010Hematology and Rheumatology Unit, Assistance Publique \u2010 H\u00f4pitaux de Paris (APHP) Necker\u2010Enfants Malades Hospital  Paris France"},{"name":"Laboratory of Immunogenetics of Pediatric Autoimmune Diseases Imagine Institute INSERM UMR 1163  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Rieux\u2010Laucat","sequence":"additional","affiliation":[{"name":"Laboratory of Immunogenetics of Pediatric Autoimmune Diseases Imagine Institute INSERM UMR 1163  Paris France"},{"name":"Laboratory of Human Genetics of Infectious Diseases, Necker Branch INSERM U1163 Necker Hospital for Sick Children, EU  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00e9r\u00e9mie","family":"Rosain","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics of Infectious Diseases, Necker Branch INSERM U1163 Necker Hospital for Sick Children, EU  Paris France"},{"name":"Study Center for Primary Immunodeficiencies Assistance Publique H\u00f4pitaux de Paris (AP\u2010HP) Necker Hospital for Sick Children, EU  Paris France"},{"name":"St.Giles Laboratory of Human Genetics of Infectious Diseases Rockefeller Branch Rockefeller University  New York USA"},{"name":"University of Paris Cit\u00e9  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Jeziorski","sequence":"additional","affiliation":[{"name":"Pathogenesis and Control of Chronic Infections INSERM U1058 Montpellier UHC University of Montpellier  Montpellier France"},{"name":"Department of General Pediatrics Infectiology, and Clinical Immunology Department of Emergency Post\u2010Emergency Department University Hospital of Montpellier  Montpellier France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bertrand","family":"Boisson","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics of Infectious Diseases, Necker Branch INSERM U1163 Necker Hospital for Sick Children, EU  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean\u2010Laurent","family":"Casanova","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics of Infectious Diseases, Necker Branch INSERM U1163 Necker Hospital for Sick Children, EU  Paris France"},{"name":"St.Giles Laboratory of Human Genetics of Infectious Diseases Rockefeller Branch Rockefeller University  New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V\u00e9ronique","family":"Fr\u00e9meaux\u2010Bacchi","sequence":"additional","affiliation":[{"name":"Department of Immunology Assistance Publique\u2010 H\u00f4pitaux de Paris (AP\u2010HP) Georges Pompidou European Hospital  Paris France"},{"name":"Inflammation, Complement and Cancer Team Cordeliers Research Center Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) Unit\u00e9 Mixte de Recherche UMRS1138  Paris France"},{"name":"COMET \u00ab Complement Expertise and Therapeutics \u00bb F\u00e9d\u00e9ration Hospitalo\u2010Universitaire  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7755-6689","authenticated-orcid":false,"given":"Carine","family":"El 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