Chronic idiopathic sensory ataxic neuropathy: immunological aspects of a series of 17 patients.
Sensory ataxic neuropathies (SANs) are characterized by loss of proprioceptive sensations and preservation of muscle strength. They may be idiopathic or associated with different toxic, infectious or autoimmune causes. Reactivity against gangliosides containing disialosyl groups, particularly GD1b, has been reported in isolated cases of acute and chronic idiopathic ataxic neuropathies (iSAN) and different experimental findings (in vivo animal models and in vitro preparations) suggest that antidisialosyl or antiGD1b antibodies could play a role in the pathogenesis of some ataxic neuropathies. We present the clinical, immunological and immunohistochemical characteristics of 17 patients who had a chronic iSAN without gammopathy. Patients were selected from a large group of 130 subjects with SAN: 93 with known etiology and 37 with iSAN. IgM and IgG antibodies to GM1, GM2, GM3, aGM1, GD1a, GD1b, GD3, GT1b and GQ1b were investigated by ELISA (INCAT protocol) and thin layer chromatography. Immunohistochemistry, using biotinylated Ig extracted from the patient&sacute; serum, was performed on human dorsal root ganglia (DRG), spinal cord, anterior and posterior roots, sural nerve and muscle tissue. The mean age of the 17 patients was 62 (37-80 years). The most disabling features were unsteadiness and severe ataxia of gait. Only one patient of this group was wheelchair-bound. The clinical data of these 17 patients were similar to those of the other patients with SAN, except that progression was slower. Antibodies to GD1b, GD3 and GT1b were found in 1/17. Two more patients (one with an acute iSAN and one with chronic iSAN and gammopathy), also had antibodies to disialosyl or GD1b. No immunohistochemical pattern of reactivity was found in any of the tissues tested with the 17 sera. In summary, this study demonstrates antidisialosyl or anti GD1b antibodies only in 3/37 (8.1p. cent) of patients with iSAN, either acute, chronic, or with gammopathy. However, their value seems to be reinforced by the negativity of antiganglioside antibodies in the large group of patients with SAN of known etiology (0/93). Further studies will be necessary to confirm the importance of target antigens containing disialosyl moieties in a subset of iSAN patients. However, the negativity of antiganglioside antibodies in most cases suggests that the pathology of the sensory neurons and/or axons is probably not humorally mediated in the majority of patients with iSAN.
Illa
I
I
Department of Neurology, Institut de Recerca, Hospital Sta Creu i Sant Pau, Universitat Autònoma de Barcelona, Spain. illa@santpau.es
Rojas
R
R
Gallardo
E
E
Serrano
C
C
Graus
F
F
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D001259:Ataxia / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology*; D002855:Chromatography, Thin Layer; D002908:Chronic Disease; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005732:Gangliosides / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index
D000888:Antibodies, Anti-Idiotypic; D005732:Gangliosides; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D016756:Immunoglobulins, Intravenous