Paroxysmal nocturnal hemoglobinuria: Test to monitor the action of eculizumab treatment.

INTRODUCTION: Paroxysmal nocturnal hemoglobinuria (PNH) is caused by a somatic mutation in the PIG-A gene, which encodes for glycosylphosphatidylinositol, a phospholipid membrane that anchors proteins like CD55 and CD59. These proteins are inhibitors of the complement-mediated lysis. PNH is diagnosed by flow cytometry, and treatment with eculizumab improves the life quality of patients with severe clinical compromise. The aim of this work was to evaluate a hemolytic test that allows monitoring the blockade of the alternative complement pathway caused by eculizumab (herein MET test). METHODS: There were analyzed a total of 163 serum samples from nine patients with PNH under treatment with eculizumab and ten healthy volunteers like controls. The patients were evaluated for 6 months. The MET test consisted in incubating red blood cells from patients (RBCPNH ) with either acidified serum from healthy volunteers and from patients with PNH. The results can be (a) Positive, (b) Blockade profile, or (c) Negative. RESULTS: Seven patients responded favorably to the eculizumab, and the test evidenced the blockade profile. The two remaining patients were nonresponders to the treatment, with a positive MET test. In these patients, the dose was increased. One responded favorably with a blockade profile, and the other continued to be nonresponder. CONCLUSIONS: The MET test proved to be a useful tool to monitor the blockade of complement by eculizumab.

Critical appraisal of eculizumab for atypical hemolytic uremic syndrome.

The biology of atypical hemolytic uremic syndrome has been shown to involve inability to limit activation of the alternative complement pathway, with subsequent damage to systemic endothelial beds and the vasculature, resulting in the prototypic findings of a thrombotic microangiopathy. Central to this process is the formation of the terminal membrane attack complex C5b-9. Recently, application of a monoclonal antibody that specifically binds to C5, eculizumab, became available to treat patients with atypical hemolytic uremic syndrome, replacing plasma exchange or infusion as primary therapy. This review focuses on the evidence, based on published clinical trials, case series, and case reports, on the efficacy and safety of this approach.