{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:51:47Z","timestamp":1791352307258,"version":"4.3.1"},"reference-count":12,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Laboratory Analysis"],"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n Protein\u2010losing enteropathy is a rarely reported feature of CD46\u2010associated disease and may resemble CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein\u2010losing enteropathy (CHAPLE) syndrome. Associated hypogammaglobulinemia may be mistaken for primary antibody deficiency.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We describe a 23\u2010year\u2010old woman with childhood\u2010onset enteropathy and hypogammaglobulinemia who had received immunoglobulin replacement for presumed common variable immunodeficiency since age 5. Multidisciplinary reassessment incorporated intestinal and renal histopathology, whole\u2010exome sequencing, family segregation, and longitudinal evaluation of the response to eculizumab.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Duodenal biopsy demonstrated intestinal lymphangiectasia, whereas kidney biopsy revealed chronic thrombotic microangiopathy with concurrent PLA2R\u2010negative membranous nephropathy. Serum C3 and C4 were within reference ranges. Sequencing identified homozygous CD46 c.565T>G (p.Tyr189Asp), with no pathogenic CD55 variant. The diagnostic laboratory reported the CD46 finding as a variant of uncertain significance. Family segregation and published functional evidence supported its clinical relevance, although patient\u2010specific functional confirmation was unavailable. Eculizumab promptly improved abdominal pain, vomiting, and oral intake. By April 2026, following dose escalation, serum albumin reached 4.3\u2009g\/dL and IgG 554\u2009mg\/dL, whereas proteinuria decreased from 5.95 to 2.4\u2009g\/day.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n This case supports considering CD46\u2010associated disease in adults with a CHAPLE\u2010like phenotype, particularly when enteric protein loss and hypogammaglobulinemia coexist with renal microangiopathy despite normal C3 and C4. The response to complement blockade supports a complement\u2010mediated disease process. Documented protein loss should prompt reassessment of a presumptive diagnosis of primary antibody deficiency.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jcla.70370","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:48:28Z","timestamp":1791352108000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CHAPLE<\/scp>\n \u2010Like Enteropathy and Renal Microangiopathy in an Adult Patient With\n CD46<\/scp>\n Deficiency"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2943-4697","authenticated-orcid":false,"given":"Bircan","family":"Erden","sequence":"first","affiliation":[{"name":"Division of Allergy and Immunology, Department of Internal Medicine, Istanbul Faculty of Medicine Istanbul University Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0225-2485","authenticated-orcid":false,"given":"Pelin","family":"Korkmaz","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology, Department of Internal Medicine, Istanbul Faculty of Medicine Istanbul University Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2526-3483","authenticated-orcid":false,"given":"Halil","family":"Yazici","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Istanbul Faculty of Medicine Istanbul University Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2262-8627","authenticated-orcid":false,"given":"Ahmet Burak","family":"Dirim","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Istanbul Faculty of Medicine Istanbul University Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5184-376X","authenticated-orcid":false,"given":"Fatih","family":"Be\u015f\u0131\u015f\u0131k","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine, Istanbul Faculty of Medicine Istanbul University Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7050-6101","authenticated-orcid":false,"given":"Nevzat","family":"Kahveci","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology, Department of Internal Medicine, Istanbul Faculty of Medicine Istanbul University Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeynep","family":"Kilinc","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology, Department of Internal Medicine, Istanbul Faculty of Medicine Istanbul University Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9741-5939","authenticated-orcid":false,"given":"Derya","family":"Unal","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology, Department of Internal Medicine, Istanbul Faculty of Medicine Istanbul University Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4256-6048","authenticated-orcid":false,"given":"Osman Ozan","family":"Yegit","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology, Department of Internal Medicine, Istanbul Faculty of Medicine Istanbul University Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9963-5916","authenticated-orcid":false,"given":"Tu\u011fba","family":"Kalayc\u0131","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Internal Medicine, Istanbul Faculty of Medicine Istanbul University Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8352-8158","authenticated-orcid":false,"given":"\u00d6zge","family":"H\u00fcrdo\u011fan","sequence":"additional","affiliation":[{"name":"Department of Pathology, Istanbul Faculty of Medicine Istanbul University Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7191-0488","authenticated-orcid":false,"given":"Yasemin","family":"\u00d6zl\u00fck","sequence":"additional","affiliation":[{"name":"Department of Pathology, Istanbul Faculty of Medicine Istanbul University Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3425-2137","authenticated-orcid":false,"given":"Melek","family":"B\u00fcy\u00fck","sequence":"additional","affiliation":[{"name":"Department of Pathology, Istanbul Faculty of Medicine Istanbul University Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3524-9952","authenticated-orcid":false,"given":"Asli","family":"Gelincik","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology, Department of Internal Medicine, Istanbul Faculty of Medicine Istanbul University Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3449-5868","authenticated-orcid":false,"given":"Semra","family":"Demir","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology, Department of Internal Medicine, Istanbul Faculty of Medicine Istanbul University Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2021.04.005"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1615887"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0902814"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005101051"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467\u2010024\u201006451\u20100"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2015.07.025"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2020.579418"},{"key":"e_1_2_8_9_1","unstructured":"National Center for Biotechnology Information \u201cClinVar; NM_172351.3(CD46):c.565T>G (p.Tyr189Asp) Variation ID 988106 VCV000988106.12 \u201daccessed August 13 2026."},{"key":"e_1_2_8_10_1","unstructured":"Alexion Pharmaceuticals Inc \u201cSOLIRIS\u00ae (Eculizumab) Injection for Intravenous Use \u201dPrescribing Information DailyMed U.S. National Library of Medicine Revised [ay\/y\u0131l] accessed [eri\u015fim tarihi \u00f6r. September 27 2026] https:\/\/dailymed.nlm.nih.gov\/dailymed\/lookup.cfm?setid=ebcd67fa\u2010b4d1\u20104a22\u2010b33d\u2010ee8bf6b9c722."},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200939392"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1208981"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000002198"}],"container-title":["Journal of Clinical Laboratory Analysis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcla.70370","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcla.70370","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcla.70370","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:48:29Z","timestamp":1791352109000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcla.70370"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,6]]},"references-count":12,"alternative-id":["10.1002\/jcla.70370"],"URL":"https:\/\/doi.org\/10.1002\/jcla.70370","archive":["Portico"],"relation":{},"ISSN":["0887-8013","1098-2825"],"issn-type":[{"value":"0887-8013","type":"print"},{"value":"1098-2825","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,6]]},"assertion":[{"value":"2026-06-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70370"}}