Comment on "Rituximab in patients with chronic inflammatory demyelinating polyradiculoneuropathy: a report of 13 cases and review of the literature"
I read with interest the paper by Benedetti et al., entitled 'Rituximab in patients with chronic inflammatory demyelinating polyradiculoneuropathy: a report of 13 cases and review of the literature'(1). Rituximab, a monoclonal antibody that binds to the CD20 antigen on B- lymphocytes, has been approved to eliminate B cell precursors, normal and malignant B cells and to reduce antibody titers (2,3). Some authors argued that the benefit of Rituximab may be exerted by reducing the pathogenic antibodies or by inducing immunoregulatory T cells (4). Chronic polyneuropathies associated with IgM paraproteinemia (almost 50% have high serum titers of anti-MAG antibodies) indicate either an underlying monoclonal gammopathy of undetermined significance (MGUS) or a malignant plasma cell dyscrasia. In chronic inflammatory demielinating poliradiculoneuropathy (CIDP), the immunopathological processes are still unclear. Benedetti et al described 13 CIDP patients, 5 without haematological disease, 4 had MGUS, 2 had lymphoma, 1 had Waldestrom macroglobulinemia and 1 had idiopathic thrombocytopenic purpura. Peripheral blood immunophenotypes before treatment have not been reported. The patient #1 (see Table 1), who had been previously described (5), had a small lymphocyitic B-cell lymphoma CD20 and the dramatic improvement after Rituximab therapy supported a role of B cells in the pathogenesis of polyneuropathy (6) The immunologic status of the other patients with CIDP has not been described in detail, placing an issue on which target rituximab acted, particularly for patients without hematologic malignancies . It is likely that patients with IgM MGUS, Waldenstrom macroglobulinemia and non-Hodgkin's lymphoma were affected by chronic polyneuropathies associated with IgM paraproteinemia, all Rituximab responsive. Electrophysiological data, available in 6 patients, have not been reported. I would like to ask the authors to provide information in order to explain that 10% changes in motor conduction velocity (MCV) values are considered as indicators of therapeutic efficacy. Recently, some authors have reported that INCAT dysability score and Medical Research Council sum score (MRC) correlated with improvement in compound muscle action potential (CMAP) amplitudes of nerves tested (7). The increase in CMAP amplitude, and not MCV, may explain the muscle strength improvement.
1. Benedetti L, Briani C, Franciotta D, Fazio R. Rituximab in patients with chronic inflammatory demyelinating polyradiculoneuropathy: a report of 13 cases and review of the literature. J Neurol Neurosurg Psychiatry. 2010 Jul 16. [Epub ahead of print]
2. Dalakas MC. B cells in the pathophysiology of autoimmune neurological disorders: a credible therapeutic target. Pharmacol Ther. 2006;112(1):57- 70
3. Dalakas MC. Invited article: inhibition of B cell functions: implications for neurology. Neurology. 2008;70(23):2252-60.
4. Dalakas MC, Rakocevic G, Salajegheh M, Dambrosia JM, Hahn AF, Raju R et al. Placebo-controlled trial of rituximab in IgM anti-myelin-associated glycoprotein antibody demyelinating neuropathy. Ann Neurol. 2009 Mar;65(3):286-93.
5. Briani C, Zara G, Zambello R et al. Rituximab-responsive CIDP. Europ J Neurol 2004;11:788-91
6. Briani C, Zambello R, Cavallaro T, Ferrari S, Lucchetta M, Pollanz S, Grisold W. Improvement of peripheral nervous system manifestations of B- cell non-Hodgkin's lymphoma after rituximab therapy. J Peripher Nerv Syst. 2009 Jun;14(2):146-8
7. Bril V, Banach M, Dalakas MC, Deng C, Donofrio P, Hanna K et al. Electrophysiologic correlations with clinical outcomes in CIDP. Muscle Nerve. 2010 Jul 21. [Epub ahead of print]
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