Successful treatment of PLA2R1-antibody positive membranous nephropathy with ocrelizumab

Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults. The disease is induced by antibodies, which are directed against the podocyte protein phospholipase A(2)receptor 1 (PLA(2)R1-ab) in 80% of cases. B cell depleting treatments, most notably rituximab, a chimeric CD20-antibody, are often effective for treatment of MN. However, in 35-40% of patients rituximab fails to induce remission of disease and relapses after rituximab-induced remission are frequent. Therefore, alternative treatment options are necessary. Over the past years optimized antibodies targeting CD20 were designed to overcome side effects or sensitization to the murine fractions of rituximab and potentially improve B cell depletion. Ocrelizumab is a humanized B cell depleting antibody, approved for treatment of multiple sclerosis (MS). Here, we report the case of a patient who was diagnosed with MS and, 8 years later, developed PLA(2)R1-associated MN. Treatment for MS was switched to the CD20-antibody ocrelizumab, which was expected to deplete B cells and potentially induce remission of MN. After treatment with ocrelizumab PLA(2)R1-ab disappeared from the circulation and the patient developed remission of proteinuria. Ocrelizumab might be an efficacious treatment alternative for patients with MN who fail to achieve remission or are immunologically sensitized to rituximab.