Introduction. Protein-losing enteropathy (PLE) manifests as hypoalbuminemia, edema, and malabsorption due to intestinal or lymphatic disruption. We studied an extended consanguineous Muslim-Arab family comprising of six patients diagnosed with PLE and hypercoagulability.
Methods. Whole exome sequencing (WES) was performed on three patients and a healthy mother. Flow cytometry was used to test for CD55 and complement overactivation. Three patients were treated by off-label compassionate eculizumab therapy, a humanized anti-C5 monoclonal antibody.
Results. WES analysis revealed a homozygous frameshift variant in CD55 (c.43del; p.Leu15Serfs*46), supported by co-segregation analysis in the extended family (n=32). Absence of CD55 was confirmed by flow cytometry. Furthermore, membrane attack complex (MAC) and iC3b depositions on WBCs were significantly increased in patients compared to age-matched controls (p<0.001). Significant clinical and laboratory improvement was observed in patients treated with eculizumab, including resolution of diarrhea, normalization of serum albumin, and 60% reduction in MAC deposition on WBCs within two months, and further ongoing improvement.
Discussion. CD55 encodes a membrane-bound complement-regulatory protein that inhibits the C3/C5 convertases and protects cells against complement-induced self-injury. The genetic findings and evidence of abnormal complement activation prompted successful off-label compassionate therapy with eculizumab, a terminal complement inhibitor. The treatment led to rapid improvement and ultimately achieved complete amelioration of symptoms in three treated patients. This path from genetic analysis to tailored therapy warrants studying the roles of complement and CD55 in other intestinal disorders that may benefit from similar treatment.
