We have recently demonstrated that early-onset Waldmann’s protein-losing enteropathy can be caused by CD55 mutations and established the pathogenic role of complement activation in intestinal lymphangiectasia and severe thromboses (CHAPLE syndrome). We sought to evaluate the therapeutic efficacy of eculizumab, a monoclonal antibody against C5 in CHAPLE patients and investigate the molecular signatures and potential biomarkers.
Fifteen patients with CHAPLE syndrome received eculizumab for a mean of 12.3 months and were carefully monitored for effects on disease and adverse events. Outcome parameters included clinical symptoms, blood chemistry, nutrition, quality of life scores, structural gastrointestinal abnormalities, and malabsorption indices. SOMALogic assay investigated pathological serum signatures of CHAPLE syndrome and their dynamic changes in response to therapy.
Eculizumab provided an immediate effect in all patients, with a gradual increase in total protein, albumin and immunoglobulin levels, which are completely restored within 4 weeks. Symptom diaries demonstrated a significant decrease in the scores of nausea, vomiting, abdominal pain and facial edema, and reduced number of bowel movements. Eculizumab reversed hematological abnormalities and intestinal malabsorption and led to a significant improvement in growth indices and overall health outcomes over time. Importantly, life threatening complications of CHAPLE syndrome were ameliorated, and patients were able to discontinue prior medications including those which were associated with significant adverse effects. Unintentional discontinuation of eculizumab longer than 6 weeks led to a relapse of symptoms. We detected major alterations in numerous biomolecules in the serum samples.
Eculizumab proved safe and highly effective in CHAPLE syndrome.