Abstract
Monoclonal antibodies are found in approximately 10% of patients with peripheral neuropathy (PN) of unknown etiology. Several autoantibodies, including anti-MAG (myelin-associated glycoprotein) antibodies, have been reported to induce neuropathy. It has been suggested that over 50% of patients with PN and IgM monoclonal gammopathy (MG) have anti-MAG IgM antibodies in their sera. This work aimed at studying the frequency and characteristics of PN in a group of Egyptian patients with MGs and to estimate the serum level of anti-MAG antibodies and its relationship to peripheral nerve dysfunction. Forty patients with MGs were enrolled in the study. Their mean age was 56.65 ± 8.55 years. There were 17 males and 23 females. Patients were subjected to complete general and neurological examination, laboratory investigations including serum LDH, β2 microglobulin, serum protein electrophoresis, urinary Bence-Jones protein, bone marrow aspiration and/or trephine biopsy, quantitative estimation of serum IgM and IgG by nephelometry, detection of anti-MAG antibodies by indirect immunofluorescence, radiological assessment and nerve conduction study of both upper and lower limbs. Clinical and electrophysiological evidences of PN were found in 32 (80%) out of the 40 patients with MG. Twenty-five patients (62.5%) had distal symmetrical polyneuropathy and seven (17.5%) had mononeuritis or mononeuritis multiplex. The majority of patients (65%) had sensory or predominantly sensorimotor polyneuropathy. The neuropathy was mainly demyelinating in 22 patients (55%) and axonal in the other 10 (25%) patients. Anti-MAG antibodies were positive in nine patients (22.5%) and six of them (66.6%) had PN. The latter was predominantly demyelinating motor neuropathy in 4 and axonal in the remaining 2. However, the relationship between the presence of anti-MAG antibodies and the development and type of PN was not statistically significant. Anti-MAG showed significant association with IgM level (P = 0.003**) and the MG subtypes: Waldenström’s macroglobulinemia (WM) and monoclonal gammopathy of undetermined significance (MGUS) (P = 0.004**). The present study showed high frequency (>60%) of distal symmetrical polyneuropathy in Egyptian patients with MG. The neuropathy was predominantly sensory and demyelinating. Anti-MAG antibodies were detected only in 22.5% of the patients, especially those with WM and MGUS and were associated with more motor and demyelinating neuropathy. We recommend that patients with chronic polyneuropathies should be evaluated for underlying plasma cell dyscrasia.
Similar content being viewed by others
References
Kyle RA, Rajkmar SV. Plasma cell disorders. Cecil textbook of medicine. 22nd ed. 2004. p. 1184–95.
Kyle RA, Theraneau TM, Rajkumar SV, et al. A long term study of prognosis in monoclonal gammopathy of undetermined significance. N Engl J Med. 2002;346:564–9.
Surveillance, Epidemiology and End Results Programme Public Use Data. Bethesda, MD: National Cancer Institute, Cancer Statistics Branch; 2004.
Ciabarra A, Latov N. Neuropathy associated with monoclonal gammopathy. Neurology. 2001. http://www.medlink.com. Accessed 2001.
Willison HJ. Anti-glycolipid antibodies in peripheral neuropathy: fact or fiction? J Neurol Neurosurg Psych. 1994;57:1303–7.
Kricka LJ, Phil D, Chem C, et al. TIETZ text book of clinical chemistry and molecular diagnostics. Opt Tech. 2006;3:85–8.
Quarles RH. Glycoproteins of the myelin sheath. J Mol Neurosci. 1997;8:1–12.
Kimura J. Electrodiagnosis in disease of nerve and muscle, 3rd ed. Oxford: Oxford University Press; 2001.
Lozeron P, Adams D. Monoclonal gammopathy and neuropathy. Curr Opin Neurol. 2007;20(5):536–41.
Kuijf ML, Eurelings M, Tio-Gillen AP, van Doorn PA, et al. Detection of anti-MAG antibodies in polyneuropathy associated with IgM monoclonal gammopathy. Neurology. 2009;73:688–95.
Gorson K, Ropper A. Axonal neuropathy associated with monoclonal gammopathy of undetermined significance. J Neurol Neurosurg Psychiatry. 1997;63:163–8.
Meucci M, Baldini L, Cappellari A, et al. Antimyelin associated glycoprotein antibodies predict the development of neuropathy in asymptomatic patients with IgM monoclonal gammopathy. Ann Neurol. 1999;46:119–22.
Goldfarb AR, Sander HW, Brannagan TH 3rd, Magda P, Latov N. Characterization of neuropathies associated with elevated IgM serum levels. J Neurol Sci. 2005;228(2):155–60.
Caudie C, Antoine JC, Viol C, et al. A trial of 117 immune mediated peripheral neuropathies associated with monoclonal IgM. Ann Biol Clin. 2006;64:353–9.
Kyle RA. Monoclonal proteins in neuropathy. Neurol Clin. 1992;10:713–34.
Dispernzieri A, Kyle RA. Neurological aspects of multiple myeloma and related disorders. Best Pract Res Clin Haematol. 2005;18:673–88.
Graces-Sanchez M, Dyck PJ, Kyle RA, et al. Anti-MAG in IgM amyloidosis may influence the expression of neuropathy in rare patients. Muscle Nerve. 2008;37:490–5.
Kuijf NL, Eurelings M, Tio-Gillen AP, et al. Detection of anti-MAG antibodies in polyneuropathy associated with IgM monoclonal gammopathy. Neurology. 2009;73(9):688–95.
Steck AJ, Kuntzer T, Erb S, et al. Polyneuropathy attributes: a comparison between patients with anti-MAG and anti-sulfatide antibodies. J Neurol. 2000;247:467–72.
Nobile-Orazio E, Marmiroli P, Baldini L, et al. Peripheral neuropathy in macroglobulinemia. Incidence and antigen specificity of M proteins. Neurology. 1987;37:1506–15.
Rajkumar SV, Kyle RA, Melton LJ, et al. Long-term follow-up of 241 patients with monoclonal gammopathy of undetermined significance: the original Mayo Clinic series 25 years later. Mayo Clinic survey 2004;79:859–66.
Matà S, Borsini W, Ambrosini S, et al. IgM monoclonal gammopathy-associated neuropathies with different IgM specificity. Eur J Neurol. 2011;18:1067–73.
Sherman WH, Latov N, Lange DJ, et al. Peripheral neuropathy and anti-MAG antibodies. CRC Neurobiol. 1988;4:301–32.
Chassande B, Leger JM, Younes-Chennoufi AB, et al. Peripheral between M protein antibody activity and clinical/electrophysiological features in 40 cases. Muscle Nerve. 1997;10:55–62.
Nobile-Orazio E, Alberto C, Alberto P. Multifocal motor neuropathy: current concepts and controversies. Muscle Nerve. 2005;31:663–80.
Steven P, Turnbull VJ, Papadobpoulus R, et al. High titer IgM anti-sulfatide in individuals with IgM paraproteinemia and associated peripheral neuropathy. Immunol Cell Biol. 2000;78:124–32.
Wilson JR, Stillsworth JD, Fisher MA. Electrodiagnostic patterns in MGUS neuropathy. Electromyogr Clin Neurophysiol. 2001;41:409–18.
Come G, Roveri I, Swan A, et al. Randomized controlled trial of intravenous immunoglobulin in IgM paraprotein associated demyelinating neuropathy. J Neurol. 2002;249:1370–7.
Levine T, Pestronk A, Florence J, et al. Peripheral neuropathies in Waldenström’s macroglobulinaemia. J Neurol Neurosurg Psychiatry. 2006;77:224–8.
Baehring JM, Hochberg EP, Raje N, Ulrickson M, Hochberg FH. Neurological manifestations of Waldenström macroglobulinemia. Nat Rev Neurol. 2008;4:547–56.
Kelly JJ. The electrodiagnostic findings in peripheral neuropathy associated with monoclonal gammopathy. Muscle Nerve. 1983;6(7):504–9.
Kelly JJ. Peripheral neuropathies associated with monoclonal gammopathies of undetermined significance. Rev Neurol Dis. 2008;5:14–22.
Dimachkie M. Polyneuropathy associated with anti-MAG IgM antibodies. Neurology. 1998. http://www.medlink.com (Medlink: Originally released July 13, 1998; last updated November 10, 2010; expires November 10, 2013).
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
El-Difrawy, M.M., Zaki, N.E., Marouf, H.M. et al. Clinical, electrophysiological and immunological study of peripheral nerves in Egyptian patients with monoclonal gammopathies. Int J Hematol 95, 71–76 (2012). https://doi.org/10.1007/s12185-011-0983-8
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12185-011-0983-8