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

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 6 out of 10 PRCA patients reached complete remission within the period from 9 months to 22 years of follow-up, in 4 patients no remission was achieved. M-gradient contained IgG (n = 9) and IgA (n = 1) oligoclones. In typing it consisted of IgGλ (n = 4), IgGκ (n = 5) and IgAκ (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.