NOVEL HOMOZYGOUS NONSENSE CD55 MUTATION CAUSING ADULT ONSET COMPLEMENT HYPERACTIVATION, ANGIOPATHIC THROMBOSIS AND PROTEIN LOSING ENTEROPATHY (CHAPLE) SYNDROME
- Dikla Adir, Israel
Abstract
Background and Aims
CHAPLE syndrome was recently described as a cause for early-onset protein losing enteropathy (PLE) and thrombosis secondary to biallelic CD55 mutation. We describe a 39-year-old female with adult onset intermittent gastrointestinal symptoms and hypoalbuminemia who was referred for evaluation of hypogammaglobulinemia.
Methods
Targeted CD55 gene sequencing, confirmatory CD55 flow assay and B and regulatory T cell (Treg) immunophenotyping.
Results
The patient presented with intermittent diarrhea and hypoalbuminemia at the age of 25. Symptoms subsided spontaneously after two years, but at the age of 35 the patient presented again with superior mesenteric vein thrombosis, PLE, hypoalbuminemia and hypogammaglobulinemia. Endoscopy studies showed occasional lymphangiectasia and physical examination was significant for peripheral edema and clubbing. Targeted CD55 sequencing was performed and revealed a novel homozygous c.976C>T mutation, resulting in C-terminus truncated protein (p.Gln326X). Accordingly, CD55 staining showed near absent CD55 expression with maternal carrier showing reduced CD55 MFI at around 50% compared to healthy control (Fig1A). In addition, B cell phenotyping showed skewed B cell maturation with reduced percent of CD38highCD24high naïve cells and most cells expressing a CD38lowCD24high memory phenotype (Fig1B). Treg phenotyping showed reduced proportion of FOXP3posCD25high cells and an increased proportion of FOXP3negCD25high activated CD4+ (Fig1C).
Conclusions
CD55 deficiency can cause adult onset PLE and could be easily screened by whole blood CD55 staining. In addition, CD55 deficiency is associated with abnormal B and Treg phenotyping. The patient is awaiting Eculizumab treatment.