Pure Red Cell Aplasia with M-Gradient: A Literature Review and Clinical Experience

Abstract

Background. Pure red cell aplasia (PRCA) is a rare syndrome characterized by a decrease of erythroid progenitor cell count in the bone marrow. M-gradient with both a light and a heavy chain types in PRCA patients is a rare phenomenon which is considered to be a specific form of the disease. Aim. To review a clinical presentation, diagnostic capabilities, and treatment outcomes of PRCA with M-gradient. Materials & Methods. The analysis included 10 patients. The most effective empirically established treatment program was 200-400 g of cyclophosphamide 2-3 times a week to a total dose of 6-10 g and loading courses of 100-120 mg of oral and 180-240 mg of intravenous prednisone daily within 5 days. On the 6th day prednisone injections were discontinued, and from the 7th day the oral dose of prednisone was gradually reduced to permanent discontinuation in 2-3 days. This treatment course was repeated 1-3 times at intervals of a week. Targeted enzyme immunoassay of M-gradient was performed in 4 patients in order to determine whether M-gradient is the sum of two antibody types, i.e. erythrokaryocyte antibodies and secondary anti-idiotype antibodies against primary antibodies. Results. The total of 7 out of 10 PRCA patients reached complete remission within the period from 9 months to 22 years of follow-up, in 3 patients no remission was achieved. M-gradient contained IgG (n = 9) and IgA (n = 1) oligoclones. In typing it consisted of IgGA (n = 4), IgGK (n = 5) and IgAK (n = 1). M-gradient enzyme immunoassay showed no primary and secondary anti-idiotype antibodies. Conclusion. The obtained results allow to regard gammopathy in PRCA as an effect of oligoclonal hyper-immunoglobulin without any pathogenetic connection between M-gradient and PRCA.