In the second part of our review the role of antecedent infections in the pathogenesis of GBS is discussed. The association with Campylobacter jejuni (C. jejuni) is highlighted and the concept of molecular mimicry, i.e., sharing of epitopes between microbes and peripheral nerve, explained. Alternative mechanisms to relate an infection with the immune-mediated neuropathy are elaborated. Current therapies of the GBS include plasma exchange, high-dose intravenous immunoglobulins, and supportive treatment directed to secondary complications. Published therapeutic trials are reviewed and future approaches are outlined. Principles of general care are also summarized.© 1995 John Wiley &Sons, Inc.

Immunopathogenesis and treatment of the Guillain-Barré syndrome--Part I.

Hemolytic-uremic syndrome is a clinical syndrome characterized by acute renal failure, microangiopathic hemolytic anemia, and thrombocytopenia that often follows infection by Shiga toxin- or verotoxin-producing strains of Escherichia coli. Because thrombocytopenia and platelet activation are hallmark features of hemolytic-uremic syndrome, we examined the ability of Shiga toxin to bind platelets by flow cytometry and high-performance thin-layer chromatography (HPTLC) of isolated platelet glycosphingolipids. By HPTLC, Shiga toxin was shown to bind globotriaosylceramide (Gb3) and a minor platelet glycolipid with an Rf of 0.03, band 0.03. In a survey of 20 human tissues, band 0.03 was identified only in platelets. In individuals, band 0.03 was expressed by 20% of donors and was specifically associated with increased platelet Gb3 expression. Based on glycosidase digestion and epitope mapping, band 0.03 was hypothesized to represent a novel glycosphingolipid, IV3-β-Galα1-4galactosylglobotetraosylceramide. Based on incidence, structure, and association with increased Gb3 expression, band 0.03 may represent the antithetical Luke blood group antigen. By flow cytometry, Shiga toxin bound human platelets, although the amount of Shiga toxin bound varied in donors. Differences in Shiga toxin binding to platelet membranes did not reflect differences in platelet Gb3 expression. In contrast, there was a loose association between Shiga toxin binding and decreasing forward scatter, suggesting that Shiga toxin and verotoxins bind more efficiently to smaller, older platelets. In summary, Shiga and Shiga-like toxins may bind platelets via specific glycosphingolipid receptors. Such binding may contribute to the thrombocytopenia, platelet activation, and microthrombus formation observed in hemolytic-uremic syndrome.

Shiga Toxin Binds Human Platelets via Globotriaosylceramide (Pk Antigen) and a Novel Platelet Glycosphingolipid

Abnormal immune responses to myelin associated glycoprotein (MAG), a component of myelin of the central and peripheral nervous system, have been suggested to play a role in the pathogenesis of multiple sclerosis (MS) and certain types of inflammatory polyneuropathy. To identify possible immunodominant MAG peptides in neuroinflammation, we examined T and B cell responses to five selected synthetic MAG peptides and myelin proteins in 21 patients with non-inflammatory polyneuropathy, 26 patients with MS, 10 optic neuritis patients and 17 healthy subjects. Enzyme-linked immunosorbent spot-forming cell assays were adopted, allowing the detection and enumeration of individual antigen responsive T and B cells in body fluids. Patients with polyneuropathy as well as those with MS had elevated levels of T and B cells recognizing MAG and its peptides. Any of the five MAG peptides under study functioned as immunodominant T and/or B cell epitope in individual subjects. None of the MAG peptides elicited a specific disease-associated T or B cell response. The enhanced T and B cell response to myelin components like MAG may play some role in initiation and/or progression of these diseases, but they could also represent secondary responses associated with myelin damage and indicate tolerization rather than autoaggressive immunity.

Multiple MAG peptides are recognized by circulating T and B lymphocytes in polyneuropathy and multiple sclerosis.

https://deepblue.lib.umich.edu/bitstream/handle/2027.42/73915/j.1537-2995.2001.41070898.x.pdf;sequence=1

Inverse expression of Pk and luke blood group antigens on human RBCS

The human P blood group system was discovered by Landsteiner and Levine (1927) when these investigators found a new antigen present on the erythrocytes of about 80% of individuals, who were typed P(+), and absent on others, who were typed P(−). The system was defined by one antibody, anti-P, and one antigen, P. Then, Levine et al. (1951,1954) discovered a new antibody recognizing an antigen, termed Tja, present on erythrocytes of everyone but very rare individuals. By 1955, 15 people in the world, members of 9 families, were known to lack Tja on their red blood cells and contain anti-Tja in their serum. Sanger (1955) found that six out of six Tj(a-) individuals were P-negative, a proportion very improbable to occur by chance. Furthermore, anti-Tja sera were able to agglutinate P-negative as well as P-positive red cells, indicating that P-negative cells share a common antigen with P-positive cells. The P blood group system was redefined in order to include these new findings: original common P(+) and P(−) phenotypes became P1 and P2, respectively, and the new rare phenotype, previously called Tja−, was termed “little p.” A new antigen, common to P1 and P2 and lacking in p individuals, was termed P. The anti-Tja antisera were found to contain anti-P1 and anti-P antibodies.

P Blood Group and Related Antigens

A panel of 897 randomly chosen Danish donors of blood groups 0 and A was tested for the LKE antigen using a human anti-LKE. In this sample, 78.7% were LKE positive, 20.6% were weakly positive, whereas 0.7% were LKE negative. These phenotype frequencies are similar to those obtained by the first discovered human alloserum and by the monoclonal anti-SSEA-4 in previous studies. The previously reported lower LKE antigen strength in group A versus group 0 donors, and the association of LKE to the P system was confirmed.

B. Møller

Papers

Phenotype frequency of LKE in the Danish population.