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We evaluated the analytical performances of a new line immunoassay (LIA) for the simultaneous detection of twelve anti-ganglioside and anti-sulfatide autoantibodies from Generic Assays, in comparison with our dot immunoassay. The LIA detected IgG and/or IgM autoantibodies against human GM1, GM2, GM3, GM4, GD1a, GD1b, GD2, GD3, GT1a, GT1b, GQ1b and sulfatide. Forty sera of patients with IgG autoantibody profiles in acute autoimmune neuropathies and 39 sera of patients with IgM autoantibody profiles in chronic autoimmune neuropathies were tested. To have a better sensitivity, 20 μL of sera instead of 10 μL were used. In these conditions, we observed a good concordance of IgG and IgM autoantibody profiles by both immunoassays. The test including novel gangliosides was easy to perform and superior for identifying autoimmune neuropathies. The data indicate that the test provides reliable simultaneous detection of autoantibodies against a large panel of human gangliosides and sulfatide with a good diagnostic usefulness in combination with clinical and electrophysiological data.

Scholz's disease or metachromatic leukodystrophy (MLD) is a lysosomal storage disease caused by a deficiency in arylsulfatase A (ARSA: EC 3.1.6.8). This enzyme is responsible for the degradation of sulfatides commonly called cerebroside-3-sulfate or 3-O-sulfogalactosylcéramide in galactocérébroside and sulfate. The success of hydrolysis of these sphingolipids by ARSA necessarily depends on the presence of saposine B forms a complex with the substrate. The pathological accumulation of sulfatides in the nervous system (myelin, neurons and glial cells) results most often neurological, mental retardation, nervous disorders, blindness. The metachromatic granules accumulated in the central nervous system and peripheral compounds are highly toxic. These are at high levels in the urine of patients affected by the MLD. Arylsulfatase A activity is collapsed in these patients. Unfortunately, the value of enzyme activity is not a predictor of clinical severity of the neuropathology. In contrast, the study of the gene that codes for the ARSA is seen as a way to diagnose the simplest and most reliable of the disease to avoid misdiagnosis due to the presence of pseudodeficit. The conventional therapeutic approaches are essentially symptomatic. They were made in order to restore the enzyme activity of arylsulfatase A and prevent the progression of the pathological accumulation of sulfatides and consequently reduce morbidity associated with MLD.

A typically distal and symmetrical, slowly progressive sensorimotor demyelinating neuropathy is caused by monoclonal IgM against myelin-associated glycoprotein (MAG) and SGPG, SGLPG glycolipids in the context of a benign IgM paraproteinemia. We studied a patient with a neuropathy that fulfilled the diagnostic criteria for CIDP in whom IgM kappa anti-MAG/SGPG/SGLPG were detected.The patient was a 57-year-old man who had developed a slowly progressive distal sensorimotor neuropathy, involving the lower then upper limbs, with cranial nerves palsies (oro-pharyngo-laryngo territory). ENMG showed a demyelinating neuropathy with a disproportionate slowing of conduction in distal segments of motor and axonal features in the lower limbs. The first routine laboratory analysis revealed negative or normal findings. Several serum protein electrophoreses were normal. The third cerebrospinal fluid examination demonstrated a moderate and late rise in CSF protein level with no cells. Monoclonal IgM-kappa against MAG/SGPG/SGLPG, was detected; anti-MAG antibody titre in the serum was 20 059 BTU (N1000). A small IgM-kappa paraprotein was identified by immunofixation. Electron microscopy failed to show nerve fibers with widening of outer lamellae of the myelin. There is no clinical improvement after different treatments, immunoglobulins IV, cortisteroids, plasma exchange, rituximab.It is not known whether this neuropathy is an atypical form of PNMAG or an CIDP associated with anti-MAG. When ENMG show a disproportionate slowing of conduction in distal segments of motor nerves, one should screen the serum with immunofixation to identify small monoclonal components. If IgM-MGUS is present, search should be undertaken for anti-MAG/SGPG/SGLPG antibodies. Diagnosis enables optimal treatment using, in severe cases, expensive current strategies with immunoglobulins IV, plasma exchange, and corticosteroids, or, in the event of no response, rituximab before resorting to more toxic drugs like cyclophosphamide.

It is well known that polyneuropathy is associated with monoclonal IgM kappa.We report the case of a 79-year-old man with lymphoma and motor neuron disease at cervical level simulating amyotrophic lateral sclerosis (ALS). Neurological deficit with inflammatory process evolved within 4 months. Electrophysiological findings showed increased and enlarged muscular potentials with neurogenic patterns. Nerve conduction velocities were normal, with neither multifocal neuropathy nor persistent conduction blocks. Besides mixed cryoglobulinemia type II, antisulfatide antibodies issued from monoclonal IgM were found. They were directed against myelin glycosphingolipids. No antiganglioside GM1 antibodies could be detected. This not only evoked ALS but also proximal motor axonopathy related with monoclonal IgM.This case suggests that antisulfatide antibodies often present in sensitive demyelinating polyneuropathy could also be involved in lower motor neuron syndrome.

Sulfogalactosylceramide (or sulfatide) has been localized in the central nervous system by indirect immunofluorescence. This glycosphingolipid belongs essentially to the myelinated areas. Nevertheless, it has also been found in ependymal cells, subpial processes and, in the cerebellum, in the Bergmann fibers. In the brain areas, known to be enriched in opiate receptors, some cells and nerve terminals are also sulfatide positive. In this latter localization, opiates were shown to selectively inhibit binding of the antisulfatide antibodies. We have also shown that antisulfatide inhibited, in vitro, the stereo-specific binding of narcotic drugs and that they antagonized the in vivo effects of morphine and beta-endorphin.

We isolated and purified the main lipids of the rat sciatic nerve. After methanolysis, fatty acids were isolated and purified by thin layer chromatography, and studied by gas chromatography. C 16 and C 18 fatty acids are the most abundant. Among the long-chain fatty acids, arachidonic acid (20:4) is present in some lipids; highly desaturated fatty acids in C 22 and C 24 are also present. In general, the fatty acids are highly saturated; cholesterol esters and ethanolamine phosphoglyceride fatty acids are highly unsaturated.