gq1b-ganglioside and Polyradiculoneuropathy--Chronic-Inflammatory-Demyelinating

Antibodies to the ganglioside GD1b have been reported in various forms of immune-mediated neuropathy, but their clinical relevance for diagnosis and prognosis is unknown. We investigated the prevalence of anti-GD1b antibodies in acute and chronic immune-mediated neuropathies, and the clinical presentation and outcome in Guillain-Barré syndrome (GBS) and Miller Fisher-GBS overlap syndrome (MF-GBS). Anti-GD1b, anti-GM1 and anti-GQ1b antibodies were tested in serum of patients with GBS (N = 165), Miller Fisher syndrome (N = 10), MF-GBS (N = 28), monoclonal gammopathy of unknown significance neuropathy (MGUS; N = 101), chronic inflammatory demyelinating polyneuropathy (N = 29), paraneoplastic syndrome with anti-Hu-associated neuropathy (PNS; N = 11), other auto-immune diseases (AID; N = 60), and healthy controls (HC; N = 60). All samples were tested by enzyme-linked immunosorbent assay according to the Inflammatory Neuropathy Cause and Treatment protocol. IgM anti-GD1b antibodies were found in GBS (N = 4; 2.4%), MGUS (N = 3; 3.0%), and PNS patients (N = 1; 9.1%). IgG anti-GD1b antibodies were found in GBS (N = 20; 12.1%) and MF-GBS (N = 4; 14.3%) patients, but not in the AID and HC group. In the combined group of MF-GBS and GBS patients ((MF-)GBS), 14/36 (38.9%) patients with IgG anti-GD1b antibodies also had IgG anti-GM1 antibodies, and IgG anti-GD1b and IgG anti-GQ1b antibodies were found in 3/29 (10.3%) patients. Patients with (MF-)GBS and anti-GD1b without anti-GM1 antibodies did not differ regarding sensory disturbances or disease severity but recovered faster regarding the ability to walk independently compared with patients without anti-GD1b antibodies (P = 0.031) and with patients with both anti-GD1b and anti-GM1 antibodies (P = 0.034). In conclusion, testing for anti-GD1b antibodies may identify a specific group of immune-mediated neuropathies and (MF-)GBS patients with only anti-GD1b antibodies tend to recover faster.

Topics: Adult; Aged; Autoantibodies; Autoantigens; Autoimmune Diseases of the Nervous System; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Immunoglobulin M; Lupus Erythematosus, Systemic; Middle Aged; Miller Fisher Syndrome; Monoclonal Gammopathy of Undetermined Significance; Paraneoplastic Polyneuropathy; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Sjogren's Syndrome

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

Intravenous immunoglobulin (IVIg) is an effective treatment in chronic inflammatory demyelinating polyneuropathy (CIDP). In most patients, the optimal IVIg dose and regime is unknown. Polyvalent immunoglobulin (Ig) G form idiotypic/anti-idiotypic antibody pairs in serum and IVIg preparations. We determined IgG dimer levels before and after IVIg treatment in CIDP patients with the aim to explore their utility to serve as a surrogate marker for treatment response.. IgG was purified from serum of five controls without treatment, as well as from serum of 16 CIDP patients, two patients with Miller Fisher syndrome (MFS), and one patient with myasthenia gravis before and after treatment with IVIg. IgG dimer levels were determined by size exclusion chromatography. IgG dimer formation was correlated with clinical response to IVIg treatment in CIDP. Re-monomerized IgG dimer fractions were analyzed for immunoreactivity against peripheral nerve tissue.. IgG dimer levels were significantly higher in post- compared to pre-IVIg infusion samples. Low post-treatment IgG dimer levels in CIDP patients were associated with clinical worsening during IVIg treatment. Re-monomerized IgG dimer fractions from CIDP patients showed immunoreactivity against peripheral nerve tissue, whereas similarly treated samples from MFS patients showed immunoreactivity against GQ1b.. Assessment of IgG dimer levels could be a novel approach to monitor CIDP patients during IVIg treatment, but further studies in larger cohorts are warranted to explore their utility to serve as a potential therapeutic biomarker for IVIg treatment response in CIDP.

Topics: Aged; Biomarkers; Dimerization; Female; Gangliosides; Humans; Immunoglobulin G; Immunoglobulins, Intravenous; Male; Middle Aged; Miller Fisher Syndrome; Myasthenia Gravis; Nerve Fibers; Peripheral Nerves; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating

Topics: Autoantibodies; Biomarkers; Enzyme-Linked Immunosorbent Assay; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Miller Fisher Syndrome; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Specimen Handling

Serum IgG antibody against LM1, the predominant ganglioside in the human peripheral nerve myelin, was found in 7 out of 140 patients with Guillain-Barré syndrome (GBS) in the acute phase, 1 out of 33 patients with chronic inflammatory demyelinating polyneuropathy (CIDP), and 2 out of 47 patients with Miller Fisher syndrome (MFS). Anti-LM1 IgM antibody was detected only in 2 patients, each with GBS and MFS. The clinical and electrophysiological features of the seven GBS patients with anti-LM1 IgG antibody in the serum were investigated. Six patients recovered to grade 1 within one month of the onset of neuropathy. Electrophysiological studies revealed demyelination in five patients, of which one had axonal damage in addition, whereas sufficient evidence of demyelination or axonal degeneration was not observed in the remaining two. Five had a respiratory tract infection before the onset of neuropathy, and also had serum anti-GQ1b IgG antibody. IgG antibody against LM1 might be involved in the pathogenetic mechanisms of GBS, as a possible demyelinating factor. Presence of both anti-GQ1b and anti-LM1 antibodies may be associated with some infectious agent(s) affecting the respiratory tract.

Topics: Antibodies, Bacterial; Autoantibodies; Campylobacter jejuni; Chromatography, Thin Layer; Gangliosides; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Miller Fisher Syndrome; Myelin Sheath; Peripheral Nerves; Peripheral Nervous System Diseases; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Respiratory Tract Infections