Ž . Journal of Neuroimmunology 94 1999 157–164 Anti-GM2 IgM antibodies: clinical correlates and reactivity with a human neuroblastoma cell line B. Cavanna, M. Carpo, R. Pedotti, E. Scarpini, N. Meucci, S. Allaria, G. Scarlato, E. Nobile-Orazio ) ‘Giorgio Spagnol’ SerÕice of Clinical Neuroimmunology, Centro Dino Ferrari, Institute of Clinical Neurology, IRCCS Ospedale Maggiore Policlinico, Via F. Sforza 35, UniÕersity of Milan, 20122 Milan, Italy Received 4 August 1998; revised 26 October 1998; accepted 13 November 1998 Abstract Anti-GM2 IgM antibodies have been reported in some patients with dysimmune neuropathy or lower motor neuron syndrome, in whom they were often associated with a concomitant reactivity with GM1. To investigate the possible clinical and pathogenetic relevance of these antibodies we measured serum anti-GM2 IgM titers by ELISA in 224 patients with different neuropathies and motor neuron Ž . disease and examined their binding to SK-N-SH neuroblastoma cells by indirect immunofluorescence IIF . High titers of anti-GM2 IgM Ž . antibodies were found in eight patients with dysimmune neuropathies including two with multifocal motor neuropathy MMN , two with Ž . Ž . purely motor demyelinating neuropathy without conduction block MN and four with Guillain–Barre syndrome GBS . In two MMN ´ patients reactivity with GM2 was associated with anti-GM1 reactivity and in one MN patient with anti-GM1, -GD1a and -GD1b reactivity. All but one patient had a concomitant reactivity with GalNAc-GD1a. Serum IgM from all positive patients intensely stained by IIF the surface of SK-N-SH neuroblastoma cells. This reactivity was blocked by serum pre-incubation with GM2, was not observed with sera from patients without anti-GM2 antibodies including those with high anti-GM1 or other anti-glycolipid antibodies, and correlated with the presence of GM2 in the SK-N-SH neuroblastoma cells. These findings indicate that anti-GM2 antibodies, though infrequent, are strictly associated with dysimmune neuropathies and suggest that SK-N-SH neuroblastoma cells can be a suitable in vitro model to study the functional and biological effects of these antibodies. q 1999 Elsevier Science B.V. All rights reserved. Keywords: Gangliosides; Antibodies; GM2; Neuropathy; Guillain–Barre syndrome; Neuroblastoma; Cell culture ´ 1. Introduction IgM antibodies directed against different gangliosides, including GM1 and, though less frequently, GD1a, GD1b and GQ1b, have been associated with different forms of neuropathy and, occasionally with motor neuron syn- Ž dromes Sadiq et al., 1990; Daune et al., 1992; Willison, 1994; Kornberg and Pestronk, 1995; Carpo et al., 1996, . 1998 . IgM reactivity with GM2 have been also described but the significance of this reactivity remains unclear as it has been so far reported in only few patients with different ) Corresponding author. Tel.: q39-02 55033836r4; Fax: q39-02 55190392; E-mail: eduardo.nobile@unimi.it form of dysimmune neuropathies or motor neuron syn- dromes, and was often associated with a concomitant Ž reactivity with GM1 Ilyas et al., 1988a,b; Kusunoki et al., 1989; Pestronk et al., 1990; Krarup et al., 1990; Salazar- Grueso et al., 1990; Yuki et al., 1992, 1996; Irie et al., . 1996; Jacobs et al., 1997 . In order to determine whether anti-GM2 IgM antibod- ies testing may have clinical usefulness in the diagnosis of peripheral nerve disorders we investigated their presence in patients with different neuropathies and motor neuron diseases. We then examined the binding of these antibod- ies to neuroblastoma cells to verify their capability to bind to the antigen in a cellular membrane context. This might clarify whether these autoantibodies may potentially bind to the antigen in vivo and if so have pathogenetic rele- vance. 0165-5728r99r$ - see front matter q 1999 Elsevier Science B.V. All rights reserved. Ž . PII: S0165-5728 98 00245-8