Beatrix Schwerer

Antibodies against gangliosides: a link between preceding infection and immunopathogenesis of GuillainBarré syndrome

Autoantibodies against gangliosides GM1 and GQ1b, characteristic cell surface glycolipids of the nervous system, are present in specific clinical types of GuillainBarré syndrome (GBS). Close associations of anti-GM1 with acute motor axonal neuropathy, and of anti-GQ1b with Miller Fisher syndrome, strongly suggest that these antibodies contribute to neuropathy pathogenesis. Immune responses against gangliosides are suspected to originate as a result of molecular mimicry between gangliosides and lipopolysaccharides of Campylobacter jejuni, the most frequent infectious trigger of GBS. Thus, antibodies against gangliosides may link C. jejuni infection with the precipitation of neurological disease.

ELISA for determination of albumin in the nanogram range: Assay in cerebrospinal fluid and comparison with radial immunodiffusion

An ELISA double antibody sandwich technique on polystyrene microtiter plates for quantitation of albumin in cerebrospinal fluid is described. Commercially available reagents are used for this assay, in which albumin in the range between 0.1-1 ng/100 microliters can easily be detected. Albumin determinations in 30 CSF samples by this method revealed concentrations of 0.1-0.8 mg/ml. Results obtained by ELISA correlated significantly with those from parallel experiments with commercially available RID assays. The ELISA described is a sensitive, simple, and expeditious assay for determination of albumin in the nanogram range and may be a promising method for routine analysis of albumin concentrations in CSF.

Ganglioside GM1, a molecular target for immunological and toxic attacks: similarity of neuropathological lesions induced by ganglioside-antiserum and cholera toxin.

SummaryGanglioside-antisera, the ganglioside GM1-ligands, cholera toxin (CT), and CT subunit B, respectively, were injected into the lumbosacral subarachnoid space of normal rats. The cytotoxic effects of the injected compounds on the peripheral and central nervous system were investigated by light and electron microscopy; the severity of CNS lesions was evaluated by quantitation of macrophages containing debris. In contrast to control sera and GM2-antiserum, antisera against a mixture of the major brain gangliosides GM1, GD1a, GD1b, and GT1b (MaBG) or against GM1 induced demyelination in spinal roots and spinal cord, as well as alterations of astroglia. CT induced the same cytotoxic effects as MaBG- and GM1-antisera, whereas CT subunit B was without effect. The ineffectiveness of GM2-antiserum is obviously due to the very low concentration of the specific binding target, GM2, on cell surfaces; that of CT subunit B to the lack of the cytotoxic operator, subunit A. Our results indicate that a similar pattern of neuropathological lesions may be effected by different cytotoxic mechanisms through attachment of the cytotoxic agent onto the cell surface via a common target molecule, and further substantiate the role of GM1-antibodies in the pathogenesis of demyelination.

Serum antibodies against glycosphingolipids in chronic relapsing experimental allergic encephalomyelitis: Demonstration by ELISA and relation to serum in vivo demyelinating activity

Sera from guinea pigs with spinal cord-induced chronic relapsing experimental allergic encephalomyelitis (crEAE) were tested for IgG antibodies against glycosphingolipids (GSL; galactocerebroside, ganglioside GM1, sulfatide) by an enzyme-linked immunosorbent assay and for in vivo demyelinating activity by infusion into the lumbosacral subarachnoid space of normal rats. In chronic stage-crEAE sera (40-200 days after sensitization) a high incidence (21/26) and high titers (up to 1:2560) of antibodies against one or more GSL coincided with a high incidence (22/26) of in vivo demyelinating activity. These results suggest an involvement of antibodies against various GSL in the process of demyelination.

Specific inhibition of mRNA accumulation for lymphokines in human T cell line Jurkat by mycobacterial lipoarabinomannan antigen.

The immunomodulatory effect of Mycobucterium tuberculosis‐derived lipoarabinomannan (LAM) on mitogen/antigen‐induced expression of mRNAs for a number of cytokines in human monocytic cell line Mono‐Mac‐6 and in T cell line Jurkat was investigated. Interestingly, LAM exhibited a down‐regulatory effect on the accumulation of mRNAs for IL‐2, IL‐3, granulocyle‐macrophage colony‐stimulating factor (GM‐CSF), and IL‐2 receptor alpha (IL‐2Rα) in T cells co‐stimulated with phytohacmagglutinin‐P (PHA) and 4β‐phorbol‐12‐myristyl‐13‐acctatc (PMA). In human Mono‐Mac‐6 cells, LAM has a weak inhibitory effect on the lipopolysaccharide (LPS)‐induced mRNA accumulation for IL‐1β, a slight stimulatory effect on mRNAs accumulation for IL‐8 and tumour necrosis factor‐alpha (TNF‐α). but clearly no effect on mRNA accumulation for intercellular adhesion molecule‐1 (ICAM‐I). These findings imply that LAM may contribute to the immunologic defects associated with a number of mycobacterial infections by modulating these mediators.

Ganglioside-induced antiganglioside antibodies from a neuropathy patient cross-react with lipopolysaccharides of Campylobacter jejuni associated with Guillain–Barré syndrome

Antiganglioside serum antibodies from a patient treated with gangliosides were examined for cross-reactivity with lipopolysaccharides (LPSs) of Campylobacter jejuni strains associated with Guillain-Barré syndrome (GBS). The patient had no preceding infection with C. jejuni and developed chronic progressive motor polyneuropathy following parenteral ganglioside treatment. Serum IgG antibodies recognised GM1 and GD1b gangliosides as well as asialo-GM1, and cross-reactivity was observed with LPSs from C. jejuni O:2, O:4, O:19 and O:41. The results give a clear indication that gangliosides and LPSs from C. jejuni serotypes associated with GBS share common epitopes.

Pathogenetic Aspects of Demyelinating Lesions in Chronic Relapsing Experimental Allergic Encephalomyelitis: Possible Interaction of Cellular and Humoral Immune Mechanisms

Publisher Summary This chapter discusses an experimental study that investigates whether the humoral immune response in chronic experimental allergic encephalomyelitis (EAE) is directed against autoantigens of the central nervous system (CNS) and whether it may play a role in the pathogenesis of inflammatory demyelinating lesions in chronic relapsing EAE. A major difference between acute and chronic experimental allergic encephalomyelitis (EAE) lesions is the extent of demyelination. Whereas acute EAE is a predominately inflammatory disease with little or no perivenous myelin destruction, the formation of large demyelinated plaques is the leading event in pathology of chronic EAE. It is now well established that acute EAE is because of a cell-mediated immunereaction against myelin basic protein (MBP). Also in chronic EAE, fluctuations of T-cell subpopulations have been noted with exacerbations of the disease. Humoral immune responses against central nervous system (CNS) antigens play little or no role in the pathogenesis of acute EAE.

LEUKOCYTE PPD-PEROXIDASE ACTIVITY WITH POLYUNSATURATED FATTY ACID HYDROPEROXIDES: NORMAL VALUES IN BATTEN'S DISEASE

Abstract— The activity of leukocyte p‐phenylenediamine (PPD)‐dependent peroxidase with respect to 3 peroxidic substrates was investigated in three patients with Battens disease (ceroid‐lipofuscinosis) as compared with normal controls: 1. The activity of PPD‐peroxidase, using H2O2 as the peroxidic substrate, was found to be normal in our patients with Battens disease. 2. PPD‐peroxidase was shown to be active towards arachidonic acid hydroperoxide (AAHPO) and linoleic acid hydroperoxide (LAHPO) as peroxidic substrates. No difference could be detected between patients and normals. 3. Determination of Michaelis constants with respect to H2O2, AAHPO and LAHPO in normal leukocytes revealed that PPD‐peroxidase was more active towards AAHPO (lower Km) than towards LAHPO. The same kinetic properties were found for PPD‐peroxidase in patients with ceroid‐lipofuscinosis.

ANTISERA AGAINST GANGLIOSIDE GM2: IMMUNOCHEMICAL AND IMMUNOHISTOLOGICAL STUDIES

Schwerer B., Lassman H. & Bernheimer H. (1982) Neuropathology and Applied Neurobiology 8, 217–226

IgA antibodies against phenolic glycolipid I from Mycobacterium leprae in serum of leprosy patients and contacts: Subclass distribution and relation to disease activity

The anti-PGL-I IgA response against phenolic glycolipid I (PGL-I) a specific surface antigen of Mycobacterium leprae, was demonstrated to be essentially of the IgA1 subclass in sera from leprosy patients and contacts. Anti-PGL-I IgA1 mean levels were found to increase significantly from the tuberculoid toward the lepromatous pole of the leprosy disease spectrum, thus resembling the predominating anti-PGL-I IgM response. Furthermore, anti-PGL-I IgA1 values were shown to increase significantly with increasing bacillary load, measured as bacillary index (BI) from skin biopsies. However, a number of BI negative leprosy patients recorded elevated anti-PGL-I IgA1 levels possibly reflecting a persistence of disease activity. Three of 28 household or family contacts of leprosy patients were detected seropositive for anti-PGL-I IgA1. Thus, our results suggest that anti-PGL-I IgA1 may be considered as an additional parameter for the early detection of infection with M. leprae.