Preliminary data provided encouraging results on efficacy and safety of B cell depletion with rituximab in active glomerulonephritis in the course of mixed cryoglobulinemia (MC).1 2
B cell oligomonoclonal expansion in peripheral blood and in bone marrow (BM) seems to be a key pathological and molecular feature in MC.3 4 Recently, renal involvement in MC has been associated with B cell clonal expansion in the BM.5 We report new data on the possible relationship between clinical efficacy of rituximab in MC nephritis and the disappearance of BM B cell clonal expansion after (month +6) rituximab administration demonstrated by molecular studies (fig 1).4
Figure 1 Bone marrow (BM) B cell expansion before and after rituximab. Bone marrow B cell expansion was evaluated in BM needle aspiration samples by semi-nested PCR using an upstream primer directed to the third framework variable (V) region of the IgH genes and downstream primers directed to the joining (J) region, as described previously.5 Samples were tested in duplicate, and the results were confirmed in repeated experiments. PCR products were analysed on 10% polyacrylamide gels stained with ethidium bromide. A clonal B cell expansion was defined by the presence of discrete, reproducible narrow band(s) within the predicted size range, while a polyclonal pattern by a ladder of bands with similar intensities or by the presence of weakly dominant bands, not become reproducible in repeated amplification. A monoclonal pattern of B cell expansion is shown at baseline in patients 1 and 2, and an oligoclonal pattern in patient 3. At 6 months after rituximab therapy the molecular pattern of B cell expansion had changed in all the three cases from clonal to polyclonal.
Three patients, two females and one male, aged 58, 62 …