CHAPLE‐Like Enteropathy and Renal Microangiopathy in an Adult Patient With CD46 Deficiency
5 affiliations
- 1Division of Allergy and Immunology, Department of Internal Medicine, Istanbul Faculty of Medicine Istanbul University Istanbul Türkiye
- 2Division of Nephrology, Department of Internal Medicine, Istanbul Faculty of Medicine Istanbul University Istanbul Türkiye
- 3Division of Gastroenterology, Department of Internal Medicine, Istanbul Faculty of Medicine Istanbul University Istanbul Türkiye
- 4Division of Medical Genetics, Department of Internal Medicine, Istanbul Faculty of Medicine Istanbul University Istanbul Türkiye
- 5Department of Pathology, Istanbul Faculty of Medicine Istanbul University Istanbul Türkiye
Abstract
Background: Protein‐losing enteropathy is a rarely reported feature of CD46‐associated disease and may resemble CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein‐losing enteropathy (CHAPLE) syndrome. Associated hypogammaglobulinemia may be mistaken for primary antibody deficiency.
Methods: We describe a 23‐year‐old woman with childhood‐onset enteropathy and hypogammaglobulinemia who had received immunoglobulin replacement for presumed common variable immunodeficiency since age 5. Multidisciplinary reassessment incorporated intestinal and renal histopathology, whole‐exome sequencing, family segregation, and longitudinal evaluation of the response to eculizumab.
Results: Duodenal biopsy demonstrated intestinal lymphangiectasia, whereas kidney biopsy revealed chronic thrombotic microangiopathy with concurrent PLA2R‐negative 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‐specific functional confirmation was unavailable. Eculizumab promptly improved abdominal pain, vomiting, and oral intake. By April 2026, following dose escalation, serum albumin reached 4.3 g/dL and IgG 554 mg/dL, whereas proteinuria decreased from 5.95 to 2.4 g/day.
Conclusion: This case supports considering CD46‐associated disease in adults with a CHAPLE‐like 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‐mediated disease process. Documented protein loss should prompt reassessment of a presumptive diagnosis of primary antibody deficiency.
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BibTeX
@article{erden2026chaplelike,
title = {{CHAPLE‐Like Enteropathy and Renal Microangiopathy in an Adult Patient With CD46 Deficiency}},
author = {Bircan Erden and Pelin Korkmaz and Halil Yazici and Ahmet Burak Dirim and Fatih Beşışık and Nevzat Kahveci and Zeynep Kilinc and Derya Unal and Osman Ozan Yegit and Tuğba Kalaycı and Özge Hürdoğan and Yasemin Özlük and Melek Büyük and Asli Gelincik and Semra Demir},
journal = {Journal of Clinical Laboratory Analysis},
year = {2026},
month = oct,
doi = {10.1002/jcla.70370},
url = {https://doi.org/10.1002/jcla.70370},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - CHAPLE‐Like Enteropathy and Renal Microangiopathy in an Adult Patient With CD46 Deficiency
AU - Bircan Erden
AU - Pelin Korkmaz
AU - Halil Yazici
AU - Ahmet Burak Dirim
AU - Fatih Beşışık
AU - Nevzat Kahveci
AU - Zeynep Kilinc
AU - Derya Unal
AU - Osman Ozan Yegit
AU - Tuğba Kalaycı
AU - Özge Hürdoğan
AU - Yasemin Özlük
AU - Melek Büyük
AU - Asli Gelincik
AU - Semra Demir
PY - 2026
DA - 2026/10/06
JO - Journal of Clinical Laboratory Analysis
DO - 10.1002/jcla.70370
UR - https://doi.org/10.1002/jcla.70370
AB - Background: Protein‐losing enteropathy is a rarely reported feature of CD46‐associated disease and may resemble CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein‐losing enteropathy (CHAPLE) syndrome. Associated hypogammaglobulinemia may be mistaken for primary antibody deficiency. Methods: We describe a 23‐year‐old woman with childhood‐onset enteropathy and hypogammaglobulinemia who had received immunoglobulin replacement for presumed common variable immunodeficiency since age 5. Multidisciplinary reassessment incorporated intestinal and renal histopathology, whole‐exome sequencing, family segregation, and longitudinal evaluation of the response to eculizumab. Results: Duodenal biopsy demonstrated intestinal lymphangiectasia, whereas kidney biopsy revealed chronic thrombotic microangiopathy with concurrent PLA2R‐negative 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‐specific functional confirmation was unavailable. Eculizumab promptly improved abdominal pain, vomiting, and oral intake. By April 2026, following dose escalation, serum albumin reached 4.3 g/dL and IgG 554 mg/dL, whereas proteinuria decreased from 5.95 to 2.4 g/day. Conclusion: This case supports considering CD46‐associated disease in adults with a CHAPLE‐like 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‐mediated disease process. Documented protein loss should prompt reassessment of a presumptive diagnosis of primary antibody deficiency.
SN - 0887-8013
SN - 1098-2825
ER -