galactocerebroside and Autoimmune-Diseases

The relationship between preceding infections and antibodies to glycolipids was investigated in 205 Japanese patients with Guillain-Barré syndrome (GBS). Serological evidence of recent Campylobacter jejuni (C. jejuni) infection was found in 45% of the patients, compared with 1% in healthy controls. In contrast, recent infection of cytomegalovirus (CMV), Mycoplasma pneumoniae (M. pneumoniae) and Epstein-Barr virus (EBV) was detected in only 5%, 2% and none of the patients, respectively. C. jejuni-associated GBS was more frequent in early spring than in other seasons. All stool specimens positive for C. jejuni isolation were obtained within 10 days after the onset of GBS symptoms. Of 13 C. jejuni isolates from GBS patients, 10 (77%) belonged to Penner serotype 19 (heat-stable, HS-19). Elevated titers of anti-GM1 antibody were found in 8 (80%) of 10 GBS patients whose C. jejuni isolates belonged to HS-19 and in none of those infected with non-HS-19 C. jejuni (P = 0.04), and in 49% of 92 patients with C. jejuni infection and 25% of patients without infection of C. jejuni, CMV, EBV, or M. pneumoniae (P = 0.0007). The frequencies of elevated antibody titers to GD1a, GD1b and GQ1b were also significantly higher in GBS patients associated with C. jejuni than those not associated with C. jejuni, CMV, EBV, and M. pneumoniae. GBS in Japan seems to be associated more frequently with C. jejuni and less frequently with CMV than in Europe and North America.

Topics: Adolescent; Adult; Aged; Antibodies, Bacterial; Antibodies, Viral; Antibody Specificity; Antigens, Bacterial; Autoantibodies; Autoimmune Diseases; Campylobacter Infections; Campylobacter jejuni; Child; Child, Preschool; Comorbidity; Cytomegalovirus Infections; Enteritis; Europe; Feces; Female; G(M1) Ganglioside; Galactosylceramides; Gangliosides; Herpesviridae Infections; Herpesvirus 4, Human; Humans; Japan; Male; Middle Aged; Molecular Mimicry; Mycoplasma pneumoniae; Pneumonia, Mycoplasma; Polyradiculoneuropathy; United States

Four of 82 patients with Guillain-Barré syndrome (GBS) and 1 of 12 with multifocal motor neuropathy (MMN), who previously had had Mycoplasma pneumoniae infections, had serum antibody to galactocerebroside (Gal-C). Two patients with GBS without mycoplasma infection also had anti-Gal-C antibody, whereas none of the normal or the disease controls had it. As Gal-C is a major glycolipid antigen in myelin, anti-Gal-C antibody may function in the pathogenesis of autoimmune demyelinative neuropathies. Mycoplasma pneumoniae appears to be an important preceding infectious agent in autoimmune neuropathies with anti-Gal-C antibody.

Topics: Antibodies; Autoimmune Diseases; Galactosylceramides; Humans; Neuromuscular Diseases; Pneumonia, Mycoplasma; Polyradiculoneuropathy

To test whether gangliosides (GA) might exert neuritogenic effects in vivo, experimental allergic neuritis (EAN) was studied clinically, neuropathologically, and immunologically in Lewis rats immunized with bovine peripheral nerve, P2 myelin protein, P2 myelin protein plus two different doses of GA, P2 with galactocerebroside (GC), and GA alone, each emulsified in adjuvant. All except the GA-treated group developed signs of EAN between days 11 and 14 after the injection. Rats immunized with P2 alone were the most severely affected. Rats given P2 plus GA and those given P2 plus GC displayed a significantly lower clinical score. Histological analysis revealed a comparable degree of inflammation of the peripheral nervous system and demyelination in the spinal nerve roots of bovine peripheral nerve- and P2-immunized rats. The P2 plus GA and P2 plus GC groups revealed similar degrees of pathology in the spinal nerve roots but the latter group stood apart from the rest in that it showed widespread peripheral nervous system changes extending distally into the sciatic nerve. Serological analysis demonstrated that P2 and GC, but not GA, elicited antibody (IgG) responses, but there was no correlation between antibody titer and clinical or histological involvement. The present data fail to support an enhancing role for gangliosides in the expression of EAN and, by extrapolation, in the Guillain-Barré syndrome, for which EAN serves as the laboratory model, and in which suggestions have been made that antibodies to GA may have pathogenetic significance.

Topics: Animals; Autoantibodies; Autoimmune Diseases; Cattle; Galactosylceramides; Gangliosides; Male; Myelin Basic Protein; Myelin P2 Protein; Neuritis, Autoimmune, Experimental; Rats; Rats, Inbred Lew; Sciatic Nerve

Serum antibodies to P2 protein, myelin basic protein (MBP) and galactocerebroside (GC) were examined to study the role of humoral factors in experimental allergic neuritis (EAN). Out of 19 outbred rabbits sensitized with peripheral nerve homogenate, 14 developed EAN and the remaining 5 rabbits did not develop the disease. Anti-P2 protein and anti-MBP antibodies were detected not only in the EAN rabbits but also in the nonresponders. On the other hand, anti-GC antibody was detected in 7 of 14 EAN rabbits but not in the nonresponders. This antibody appeared near the onset of the clinical signs. As 7 rabbits developed EAN in the absence of the antibody and the titer did not correlate with the clinical severity, it is unlikely that anti-GC antibody is the major factor in inducing EAN. However, this antibody, along with other factors, may play a role in EAN.

Topics: Animals; Autoantibodies; Autoimmune Diseases; Cerebrosides; Galactosylceramides; Myelin Basic Protein; Myelin P2 Protein; Neuritis, Autoimmune, Experimental; Peripheral Nerves; Rabbits; Time Factors

To study the demyelinative effects of antibodies to glycolipids, well-myelinated cultures of mouse spinal cord tissue were exposed to antisera against galactocerebroside and two gangliosides (GM1 and GM4), as well as to anti-white matter antiserum. The demyelinative process was evaluated by morphologic and biochemical techniques. Cultures exposed to anti-white matter and anti-galactocerebroside antisera showed the most marked changes. These consisted of a decrease in the number of oligodendroglial cells and dissolution and phagocytosis of myelin. Concomitantly, the activity of 2',3'-cyclic nucleotide-3'-phosphohydrolase (CNPase) was decreased by 60-70%. This occurred within 24 h of exposure to a relatively low concentration of serum (10%). Cultures exposed to anti-GM1 and anti-GM4 antisera showed similar changes but to a lesser degree. The CNPase activity was decreased about 30% within 48 h of exposure to a 25% concentration of these antisera. This diminution represents about a 20% loss of myelin, an observation corroborated by electron microscopy where myelin but not oligodendroglial cell loss was observed. Therefore, in addition to anti-galactocerebroside activity, which was previously found to be the major antibody responsible for the demyelinating activity induced by anti-whole CNS tissue antiserum, these data suggest that antibodies to gangliosides like GM1 and GM4 might also play a role in immune-mediated demyelination, including perhaps, the human demyelinating diseases.

Topics: Animals; Autoimmune Diseases; Culture Techniques; Demyelinating Diseases; G(M1) Ganglioside; Galactosylceramides; Gangliosides; Glycolipids; Immune Sera; Mice; Microscopy, Electron; Spinal Cord