i(3)so3-galactosylceramide and Polyneuropathies

Treatment of immune-mediated neuropathies first requires an accurate diagnosis. The diagnosis is often based on clinical, electrophysiological, and immunological features of the syndrome. The selection of appropriate therapies is then based on the spectrum of response of a syndrome to medications and an assessment of possible side effects. In neuropathies with associated serum immunoglobulin M autoantibodies, such as anti-myelin-associated glycoprotein and motor syndromes, the choices of therapy are often limited to cytotoxic agents and, in some cases, intravenous immunoglobulin. In neuropathies with immunoglobulin G antibodies in both serum and cerebrospinal fluid, such as sensory neuronopathies associated with anti-Hu antibodies, there is no well-documented response to any immunotherapy. The general principles regarding therapy of immune neuropathies will be discussed with a focus on diagnosis and treatment options of the demyelinating and immunoglobulin M antibody-associated neuropathies.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Autoantibodies; Cyclophosphamide; Demyelinating Diseases; Humans; Immunoglobulin M; Immunoglobulins, Intravenous; Immunosuppressive Agents; Myelin-Associated Glycoprotein; Neuromuscular Diseases; Polyneuropathies; Rituximab; Sulfoglycosphingolipids

Of the eight clinically defined neuropathies associated with HIV infection, there is compelling evidence that acute and chronic inflammatory demyelinating polyneuropathy (IDPN) have an autoimmune pathogenesis. Many non-HIV infected individuals who suffer from sensory-motor nerve dysfunction have autoimmune indicators. The immunopathogenesis of demyelination must involve neuritogenic components in myelin. The various antigens suspected to play a role in HIV-seronegative IDPN include (i) P2 protein; (ii) sulfatide (GalS); (iii) various gangliosides (especially GM1); (iv) galactocerebroside (GalC); and (v) glycoproteins or glycolipids with the carbohydrate epitope glucuronyl-3-sulfate. These glycoproteins or glycolipids may be individually targeted, or an immune attack may be raised against a combination of any of these epitopes. The glycolipids, however, especially GalS, have recently evoked much interest as mediators of immune events underlying both non-HIV and HIV-associated demyelinating neuropathies. The present review outlines the recent research findings of antiglycolipid antibodies present in HIV-infected patients with and without peripheral nerve dysfunction, in an attempt to arrive at some consensus as to whether these antibodies may play a role in the immunopathogenesis of HIV-associated inflammatory demyelinating polyneuropathy.

Topics: Animals; Gangliosides; Glycolipids; HIV Infections; Humans; Myelin Sheath; Polyneuropathies; Polyradiculoneuropathy; Sulfoglycosphingolipids

We performed a serological investigation using glycoarray in Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and multifocal motor neuropathy (MMN). Antibodies to 10 glycolipids and 45 glycolipid complexes were tested. Anti-GM1/sulfatide and anti-GA1/sulfatide IgG antibodies were common in GBS (20.0% and 19.0%, respectively). Anti-GQ1b/sulfatide IgG antibody was detected in 14.0% of GBS patients. IgG antibodies to antigens containing GQ1b were significantly correlated with ophthalmoplegia in GBS (p<0.01). IgM antibodies to antigens containing GM1 or GalNAc-GD1a were in 50% and 37.5% of MMN patients, respectively. Glycoarray is efficient for detecting antibodies against numerous glycolipid complexes in immune-mediated neuropathies.

Topics: Adult; Aged; Aged, 80 and over; Autoantibodies; Enzyme-Linked Immunosorbent Assay; Female; Gangliosides; Glycolipids; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Japan; Male; Middle Aged; Polyneuropathies; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Statistics, Nonparametric; Sulfoglycosphingolipids; Young Adult

IgM paraproteins often present reactivity to myelin-associated glycoprotein (MAG) and sulfatide. We describe the clinical and neurophysiological findings, and therapy response in 21 patients with IgM paraproteinemic neuropathy (15 with anti-MAG antibodies, 1 with anti-sulfatide antibodies, and 5 with both reactivity), and in 2 with anti-sulfatide positivity and no hematological disease. All patients complained of sensory symptoms, the majority had demyelinating neuropathy. Indirect immunofluorescence on human normal sural nerves disclosed different staining patterns. Eight of 13 patients (6 anti-MAG, 1 anti-sulfatide, 1 both anti-sulfatide and anti-MAG antibodies) improved after Rituximab. IVIg, steroids and plasma-exchange were also administered with different responses.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Murine-Derived; Autoantibodies; Humans; Infusions, Intravenous; Middle Aged; Myelin-Associated Glycoprotein; Polyneuropathies; Rituximab; Sulfoglycosphingolipids; Sural Nerve; Treatment Outcome

Phospholipids are abundantly represented within the nervous system. Aim of our study was to evaluate the presence and fine specificity of anti phospholipid antibodies (aPLAb) among patients with monoclonal gammopathy associated neuropathy. Thirty nine percent of these patients had high titers of aPLAb, mostly associated with low levels of anti beta2 glycoprotein I, which suggests different antibody specificity compared to patients with anti phospholipid syndrome. Further 6/48 patients with dysimmune neuropathy without monoclonal gammopathy had positive aPLAb titers. APLAb strongly cross-reacted with sulfatide. These findings suggest an adjuntive role of aPLAb on nerve damage and may help to better understand the nerve binding properties of anti-sulfatide antibodies.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Antiphospholipid; Antibody Specificity; Autoantibodies; beta 2-Glycoprotein I; Cross Reactions; Female; Humans; Male; Middle Aged; Movement Disorders; Nervous System Diseases; Paraproteinemias; Polyneuropathies; Prospective Studies; Sensation Disorders; Sulfoglycosphingolipids

Topics: Age of Onset; Autoantibodies; Gait Ataxia; Humans; Polyneuropathies; Sulfoglycosphingolipids; Syndrome

To determine threshold titers and diagnostic accuracy of anti-GM1 and anti-sulfatide antibodies (Ab) for autoimmune polyneuropathies (PN) in overall and for particular subtypes of them.. In this study 84 PN patients, 120 epileptics and 93 healthy controls' sera were tested by enzyme-linked immunosorbent assay for autoAbs and results confirmed by thin-layer chromatography. Frequencies of positive patients at increasing cut-off were compared to determine threshold titers. Accuracy was determined by Receiver Operator Characteristic analysis.. A 1:2,000 titer for IgM anti-GM1 and a 1:4,000 titer for IgM anti-sulfatide Ab resulted to be threshold titers for autoimmune PN in overall. IgM anti-GM1 and anti-sulfatide Ab had low discriminating capacity between autoimmune PN and other PN, but good discriminating capacity between motor neuropathy (for anti-GM1 Ab) or PN in IgM-paraproteinemia or chronic painful sensory axonal PN (for anti-sulfatide Ab) and other PN.. Our results suggest that testing IgM anti-GM1 or anti-sulfatide Ab is useful only for diagnostic confirmation of specific subtypes of autoimmune PN.

Topics: Aged; Antibody Formation; Autoimmune Diseases; Diagnosis, Differential; Female; Gangliosidosis, GM1; Humans; Immunoglobulin M; Male; Middle Aged; Polyneuropathies; Reference Values; Sensitivity and Specificity; Sulfoglycosphingolipids

Topics: Autoantibodies; Demyelinating Diseases; G(M1) Ganglioside; Heart Transplantation; Humans; Immunosuppression Therapy; Male; Middle Aged; Polyneuropathies; Sulfoglycosphingolipids

Sera from 53 patients with acute Guillain-Barré syndrome (GBS), 15 patients with chronic inflammatory demyelinating polyneuropathy (CIDP), 13 patients with other neurological diseases (OND) and 31 healthy controls were tested for IgM and IgG antibodies to sulfoglucuronyl paragloboside (SGPG) and sulfatide by both an ELISA and a thin-layer chromatogram-overlay technique. Although the mean levels of anti-SGPG or anti-sulfatide antibodies in GBS patients were not elevated compared to controls, the occurrence of anti-SGPG antibodies was more frequent in GBS patients than in controls (P less than 0.02). Acute GBS patients with antibodies to SGPG or sulfatide were clinically indistinguishable from other GBS patients. Our data suggest that elevated levels of antibodies to SGPG could be important in the pathogenesis of neuropathy in some GBS patients.

Topics: Animals; Autoantibodies; Carbohydrate Sequence; Cats; Enzyme-Linked Immunosorbent Assay; Female; Gangliosides; Glycolipids; Humans; Immunoglobulin G; Immunoglobulin M; Male; Middle Aged; Molecular Sequence Data; Nervous System Diseases; Polyneuropathies; Polyradiculoneuropathy; Sulfoglycosphingolipids