Skip to main content
PMC home page
Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 2003 Apr;74(4):485–489. doi: 10.1136/jnnp.74.4.485

Treatment of IgM antibody associated polyneuropathies using rituximab

A Pestronk 1, J Florence 1, T Miller 1, R Choksi 1, M Al-Lozi 1, T Levine 1
PMCID: PMC1738397  PMID: 12640069

Abstract

Objectives: Polyneuropathies with associated serum IgM antibodies are often difficult to treat. Rituximab is a monoclonal antibody directed against the B cell surface membrane marker CD20. Rituximab eliminates B cells from the circulation, and, over time, could reduce cells producing autoantibodies. This study tested the ability of rituximab to produce changes in serum antibody titres, and improvement in strength, in patients with neuromuscular disorders and IgM autoantibodies.

Methods: Over a period of two years, the authors evaluated changes in strength, measured by quantitative dynamometry, and concentrations of several types of serum antibodies in patients with polyneuropathies and serum IgM autoantibodies. Twenty one patients treated with rituximab were compared with 13 untreated controls.

Results: Treatment with rituximab was followed by improved strength (an increase of mean (SEM) 23% (2%)of normal levels of strength), a reduction in serum IgM autoantibodies (to 43% (4%) of initial values), and a reduction in total levels of IgM (to 55% (4%) of initial values). There was no change in levels of serum IgG antibodies. There were no major side effects, even though B cells were virtually eliminated from the circulation for periods up to two years.

Conclusions: In patients with IgM autoantibody associated peripheral neuropathies, rituximab treatment is followed by reduced serum concentrations of IgM, but not IgG, antibodies, and by improvement in strength. Additional studies, with placebo controls and blinded outcome measures, are warranted to further test the efficacy of rituximab treatment of IgM associated polyneuropathies.

Full Text

The Full Text of this article is available as a PDF (132.7 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beck M., Giess R., Würffel W., Magnus T., Ochs G., Toyka K. V. Comparison of maximal voluntary isometric contraction and Drachman's hand-held dynamometry in evaluating patients with amyotrophic lateral sclerosis. Muscle Nerve. 1999 Sep;22(9):1265–1270. doi: 10.1002/(sici)1097-4598(199909)22:9<1265::aid-mus15>3.0.co;2-f. [DOI] [PubMed] [Google Scholar]
  2. Blume G., Pestronk A., Goodnough L. T. Anti-MAG antibody-associated polyneuropathies: improvement following immunotherapy with monthly plasma exchange and IV cyclophosphamide. Neurology. 1995 Aug;45(8):1577–1580. doi: 10.1212/wnl.45.8.1577. [DOI] [PubMed] [Google Scholar]
  3. Elliott J. L., Pestronk A. Progression of multifocal motor neuropathy during apparently successful treatment with human immunoglobulin. Neurology. 1994 May;44(5):967–968. doi: 10.1212/wnl.44.5.967. [DOI] [PubMed] [Google Scholar]
  4. Erb S., Ferracin F., Fuhr P., Rösler K. M., Hess C. W., Kuntzer T., Bogousslavsky J., Sztajzel R., Steck A. J. Polyneuropathy attributes: a comparison between patients with anti-MAG and anti-sulfatide antibodies. J Neurol. 2000 Oct;247(10):767–772. doi: 10.1007/s004150070090. [DOI] [PubMed] [Google Scholar]
  5. Federico P., Zochodne D. W., Hahn A. F., Brown W. F., Feasby T. E. Multifocal motor neuropathy improved by IVIg: randomized, double-blind, placebo-controlled study. Neurology. 2000 Nov 14;55(9):1256–1262. doi: 10.1212/wnl.55.9.1256. [DOI] [PubMed] [Google Scholar]
  6. Feldman E. L., Bromberg M. B., Albers J. W., Pestronk A. Immunosuppressive treatment in multifocal motor neuropathy. Ann Neurol. 1991 Sep;30(3):397–401. doi: 10.1002/ana.410300312. [DOI] [PubMed] [Google Scholar]
  7. Iacona I., Lazzarino M., Avanzini M. A., Rupolo M., Arcaini L., Astori C., Lunghi F., Orlandi E., Morra E., Zagonel V. Rituximab (IDEC-C2B8): validation of a sensitive enzyme-linked immunoassay applied to a clinical pharmacokinetic study. Ther Drug Monit. 2000 Jun;22(3):295–301. doi: 10.1097/00007691-200006000-00010. [DOI] [PubMed] [Google Scholar]
  8. Johnson P. W., Glennie M. J. Rituximab: mechanisms and applications. Br J Cancer. 2001 Nov 30;85(11):1619–1623. doi: 10.1054/bjoc.2001.2127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Levine T. D., Pestronk A. IgM antibody-related polyneuropathies: B-cell depletion chemotherapy using Rituximab. Neurology. 1999 May 12;52(8):1701–1704. doi: 10.1212/wnl.52.8.1701. [DOI] [PubMed] [Google Scholar]
  10. Lopate Glenn, Choksi Rati, Pestronk Alan. Severe sensory ataxia and demyelinating polyneuropathy with IgM anti-GM2 and GalNAc-GD1A antibodies. Muscle Nerve. 2002 Jun;25(6):828–836. doi: 10.1002/mus.10122. [DOI] [PubMed] [Google Scholar]
  11. Léger J. M., Chassande B., Musset L., Meininger V., Bouche P., Baumann N. Intravenous immunoglobulin therapy in multifocal motor neuropathy: a double-blind, placebo-controlled study. Brain. 2001 Jan;124(Pt 1):145–153. doi: 10.1093/brain/124.1.145. [DOI] [PubMed] [Google Scholar]
  12. McLaughlin P., Grillo-López A. J., Link B. K., Levy R., Czuczman M. S., Williams M. E., Heyman M. R., Bence-Bruckler I., White C. A., Cabanillas F. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol. 1998 Aug;16(8):2825–2833. doi: 10.1200/JCO.1998.16.8.2825. [DOI] [PubMed] [Google Scholar]
  13. Nobile-Orazio E., Cappellari A., Meucci N., Carpo M., Terenghi F., Bersano A., Priori A., Barbieri S., Scarlato G. Multifocal motor neuropathy: clinical and immunological features and response to IVIg in relation to the presence and degree of motor conduction block. J Neurol Neurosurg Psychiatry. 2002 Jun;72(6):761–766. doi: 10.1136/jnnp.72.6.761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Nobile-Orazio E., Meucci N., Baldini L., Di Troia A., Scarlato G. Long-term prognosis of neuropathy associated with anti-MAG IgM M-proteins and its relationship to immune therapies. Brain. 2000 Apr;123(Pt 4):710–717. doi: 10.1093/brain/123.4.710. [DOI] [PubMed] [Google Scholar]
  15. Nobile-Orazio E. Multifocal motor neuropathy. J Neuroimmunol. 2001 Apr 2;115(1-2):4–18. doi: 10.1016/s0165-5728(01)00266-1. [DOI] [PubMed] [Google Scholar]
  16. Ortiz N., Rosa R., Gallardo E., Illa I., Tomas J., Aubry J., Sabater M., Santafé M. IgM monoclonal antibody against terminal moiety of GM2, GalNAc-GD1a and GalNAc-GM1b from a pure motor chronic demyelinating polyneuropathy patient: effects on neurotransmitter release. J Neuroimmunol. 2001 Sep 3;119(1):114–123. doi: 10.1016/s0165-5728(01)00373-3. [DOI] [PubMed] [Google Scholar]
  17. Pestronk A., Choksi R. Multifocal motor neuropathy. Serum IgM anti-GM1 ganglioside antibodies in most patients detected using covalent linkage of GM1 to ELISA plates. Neurology. 1997 Nov;49(5):1289–1292. doi: 10.1212/wnl.49.5.1289. [DOI] [PubMed] [Google Scholar]
  18. Pestronk A., Li F., Bieser K., Choksi R., Whitton A., Kornberg A. J., Goldstein J. M., Yee W. C. Anti-MAG antibodies: major effects of antigen purity and antibody cross-reactivity on ELISA results and clinical correlation. Neurology. 1994 Jun;44(6):1131–1137. doi: 10.1212/wnl.44.6.1131. [DOI] [PubMed] [Google Scholar]
  19. Pestronk A., Lopate G., Kornberg A. J., Elliott J. L., Blume G., Yee W. C., Goodnough L. T. Distal lower motor neuron syndrome with high-titer serum IgM anti-GM1 antibodies: improvement following immunotherapy with monthly plasma exchange and intravenous cyclophosphamide. Neurology. 1994 Nov;44(11):2027–2031. doi: 10.1212/wnl.44.11.2028. [DOI] [PubMed] [Google Scholar]
  20. Pestronk A. Multifocal motor neuropathy: diagnosis and treatment. Neurology. 1998 Dec;51(6 Suppl 5):S22–S24. doi: 10.1212/wnl.51.6_suppl_5.s22. [DOI] [PubMed] [Google Scholar]
  21. Stasi R., Pagano A., Stipa E., Amadori S. Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura. Blood. 2001 Aug 15;98(4):952–957. doi: 10.1182/blood.v98.4.952. [DOI] [PubMed] [Google Scholar]
  22. Treon Steven P., Agus David B., Link Brian, Rodrigues Gilberto, Molina Arturo, Lacy Martha Q., Fisher David C., Emmanouilides Christos, Richards Arthur I., Clark Bruce. CD20-Directed Antibody-Mediated Immunotherapy Induces Responses and Facilitates Hematologic Recovery in Patients With Waldenstrom's Macroglobulinemia. J Immunother (1991) 2001 May;24(3):272–279. [PubMed] [Google Scholar]
  23. Van den Berg-Vos R. M., Franssen H., Wokke J. H. J., Van den Berg L. H. Multifocal motor neuropathy: long-term clinical and electrophysiological assessment of intravenous immunoglobulin maintenance treatment. Brain. 2002 Aug;125(Pt 8):1875–1886. doi: 10.1093/brain/awf193. [DOI] [PubMed] [Google Scholar]
  24. Zaja F., Russo D., Fuga G., Perella G., Baccarani M. Rituximab for myasthenia gravis developing after bone marrow transplant. Neurology. 2000 Oct 10;55(7):1062–1063. doi: 10.1212/wnl.55.7.1062-a. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Neurology, Neurosurgery, and Psychiatry are provided here courtesy of BMJ Publishing Group

RESOURCES