Journal of clinical laboratory analysis · 2026
CHAPLE-Like Enteropathy and Renal Microangiopathy in an Adult Patient With CD46 Deficiency.
Клинический случайСтатьяНазвание и аннотация: Перевод пока не подготовлен
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Erden Bircan, Korkmaz Pelin, Yazici Halil, Dirim Ahmet Burak, Beşışık Fatih, Kahveci Nevzat, Kilinc Zeynep, Unal Derya, Yegit Osman Ozan, Kalaycı Tuğba, Hürdoğan Özge, Özlük Yasemin, Büyük Melek, Gelincik Asli, Demir Semra
Аннотация
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.
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.