Antibodies to Campylobacter jejuni react with myelin proteins of the central nervous system.
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Antibodies, Bacterial↗
Biomedical subjects
H Bernheimer
Publications and source records attributed to H Bernheimer.
Detection of IgA anti-PGL-I specific antigen to Mycobacterium leprae in mangabey monkeys inoculated with M. leprae.
Using sera from 4 pairs of mangabey monkeys inoculated with titrated doses of Mycobacterium leprae we demonstrated that IgA antibodies against M. leprae specific PGL-I antigen were present in 75% of inoculated monkey's sera. High IgA antibody was detected in 50% (3/6) of infected animals and all three developed lepromatous leprosy (LL). Antibody titers correlated with PGL-I antigen in serum. The highest IgA peak appeared late and corresponded to the beginning of treatment, and in two of them appeared shortly after or corresponded with neurological damage. Low IgA response was found in the other 3 monkeys (50%-3/6), two of which developed indeterminate leprosy (I) and the other one LL. Low IgA levels appeared late after IgG and IgM, and shortly after neurologic signs. Both I monkeys were negative for PGL-I in serum. The remaining 2 monkeys (25%-2/8) did not show an IgA response; one of them developed LL but the disease regressed to I. IgM seemed to correspond to the appearance of PGL-I in serum. The other animal did not develop clinical symptoms of leprosy, and PGL-I in serum was negative. Although there was no clear relation between the development of anti-PGL-I IgA and experimental leprosy, the finding of a high IgA response in some animals suggests that further studies are needed to evaluate the role of antigen-specific IgA in the disease process.
Animals↗
X-linked adrenoleukodystrophy (ALD): a novel mutation of the ALD gene in 6 members of a family presenting with 5 different phenotypes.
Fragments of the adrenoleukodystrophy (ALD) cDNA from a patient with adolescent ALD were amplified by polymerase chain reaction and subcloned. Bidirectional sequencing of the entire coding ALD gene disclosed a cytosine to guanine transversion at nucleotide 1451 in exon five, resulting in substitution of proline 484 by arginine. Five of nine siblings of the patient, comprising two cerebral ALD, one adrenomyeloneuropathy, one Addison only as well as the symptomatic mother (all accumulating very long chain fatty acids) carried this mutation, which was not found in the unaffected persons, in five unrelated ALD patients, and in twenty controls. We propose that this missense mutation generated the disease per se as well as the metabolic defect; the different phenotypes, however, must have originated by means of additional pathogenetic factors.
Adolescent↗
Chronic progressive motor polyneuropathy after ganglioside treatment.
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Adult↗
GM 1 antibodies in Guillain-Barré syndrome: isotypes, course and clinical outcome.
IgA, IgG, and IgM antibodies against ganglioside GM 1 were investigated in sera of 15 patients with Guillain-Barré syndrome (GBS), as compared with healthy controls. Significantly raised titers were found in 4 patients who showed persisting weakness due to muscle wasting (3 patients) or due to the development of a chronic relapsing form of GBS (1 patient) after a follow up period of 1 year. By contrast, only 1 out of 11 anti-GM 1 seronegative patients showed persisting muscle wasting. In 1 patient with GBS following Campylobacter jejuni enteritis an IgA anti-GM 1 immune response was found to predominate, suggesting that this immune response may be due to crossreactivity between GM 1 and Campylobacter antigens. We conclude that elevated antibody titers against ganglioside GM 1 may be a valuable marker to predict poor motor recovery in GBS.
Activities of Daily Living↗
Unusual orthochromatic leukodystrophy with epitheloid cells (Norman-Gullotta): increase of very long chain fatty acids in brain discloses a peroxisomal disorder.
Very long chain fatty acids (VLCFA) were found to be markedly increased and phytanic acid was borderline above normal in formalin-fixed brain white matter of case with an unusual type of familial leukodystrophy with epitheloid cells as described previously by Gullotta et al. [Neuropädiatrie (1970) 2: 173-186]. Increased VLCFA in brain clearly demonstrate that the patient had suffered from a peroxisomal disease. This diagnosis is corroborated by ultrastructural findings in brain showing typical lamellar inclusions. The particular type of peroxisomal disorder present in case (heterozygote of X-linked adrenoleukodystrophy?) remains speculative.
Adrenoleukodystrophy↗
Simultaneous detection of the two most frequent metachromatic leukodystrophy mutations.
Metachromatic leukodystrophy (MLD) is an autosomal recessive neurometabolic disorder caused by deficiency of arylsulfatase A (ASA). To detect ASA mutations E2S609 and E8P2382, the two most frequent MLD mutations, a non-radioactive polymerase chain reaction (PCR)-based assay was developed. This assay is a multiple "mutated primer-modulated PCR restriction fragment length polymorphism". The primers related to each mutation mismatch to create an XbaI or PstI restriction site in mutation E2S609 or E8P2382, respectively. The assay was designed to give four fragments of 160, 130, 100, and 70 bp, easy to distinguish. An internal control fragment is not necessary since both primer pairs amplify different regions of the ASA gene and fragments will be obtained in all allelic possibilities. This technique produced clear-cut results when genomic DNA, isolated either from leukocytes, cultured human fibroblasts, or paraffin-embedded autopsy material, was used as template. The assay will be of help in comparative studies on the relation between MLD genotype and phenotype, a problem not yet fully understood. Since our method was shown to work also on DNA from paraffin-embedded autopsy material, genotype/phenotype studies would not be restricted to in vivo investigations but could be done also on post mortem material, thus including investigations on a large group of cases and also studies on the relation between genotype and neuropathological features.
Base Sequence↗
Specific inhibition of mRNA accumulation for lymphokines in human T cell line Jurkat by mycobacterial lipoarabinomannan antigen.
The immunomodulatory effect of Mycobacterium 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, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-2 receptor alpha (IL-2R alpha) in T cells co-stimulated with phytohaemagglutinin-P (PHA) and 4 beta-phorbol-12-myristyl-13-acetate (PMA). In human Mono-Mac-6 cells. LAM has a weak inhibitory effect on the lipopolysaccharide (LPS)-induced mRNA accumulation for IL-1 beta, a slight stimulatory effect on mRNAs accumulation for IL-8 and tumour necrosis factor-alpha (TNF-alpha), but clearly no effect on mRNA accumulation for intercellular adhesion molecule-1 (ICAM-1). These findings imply that LAM may contribute to the immunologic defects associated with a number of mycobacterial infections by modulating these mediators.
Antigens, Bacterial↗
[Peroxisomal neurologic diseases and Refsum disease: very long chain fatty acids and phytanic acid as diagnostic markers].
Peroxisomal disorders are genetic metabolic diseases with generalized, multiple, or single functional disturbances of the peroxisome. According to the extent of the functional disturbances 3 groups of diseases can be differentiated: disorders with generalized loss of peroxisomal functions (Zellweger syndrome, ZS; neonatal adrenoleukodystrophy, NALD; infantile Refsum's disease), disorders with multiple enzymatic defects (e.g. rhizomelic chondrodysplasia punctata), and disorders with a single enzymatic defect in the peroxisome, the most important being adrenoleukodystrophy/adrenomyeloneuropathy (ALD/AMN). Adult Refsum's disease, a genetic neurological disorder with phytanic acid accumulation, is due to a mitochondrial enzyme deficiency, but is often considered together with peroxisomal diseases because of phytanic acid (PHYT) accumulation in most peroxisomal diseases. The main clinical and pathological criteria of the major disorders and the biochemical parameters of their differentiation are presented. Elevated levels of very long chain fatty acids (VLCFA) and/or PHYT are the primary diagnostic markers for all peroxisomal disorders and adult Refsum's disease, respectively. Our investigations disclosed 30 ALD/AMN hemizygotes, 16 ALD/AMN heterozygotes, 8 cases of ZS/NALD and 7 patients with adult Refsum's disease. In addition, 15 cases of peroxisomal disorders were confirmed by biochemical investigations in autopsy material. With regard to peroxisomal disorders, therapeutic concepts exist only for ALD/AMN: corticosteroid substitution for adrenal insufficiency, dietary treatment, and bone marrow transplantation (BMT). Adult Refsum's disease can be treated successfully by dietary therapy. In case of dietary treatment and BMT, assay of VLCFA and/or PHYT is important for the biochemical evaluation of these therapies.
Adolescent↗
Serum antibodies against peripheral nervous system antigens in leprosy.
Since antibodies against peripheral nervous system (PNS) antigens may play a pathogenetic role in the mechanism of nerve damage in leprosy, sera from leprosy patients and contacts were investigated for anti-PNS antibodies by ELISA and immunoblot. In ELISA, elevated anti-PNS antibody levels were detected in 4 of 98 (4.1%) leprosy patients (4 of 52, 7.7%, lepromatous leprosy patients), in 1 of 28 (3.6%) contacts, and in 1 of 18 (5.6%) normal controls. There was no correlation between anti-PNS antibody levels and the bacterial index or neuropathy in leprosy. Immunoblot with a sample of six leprosy and five control sera showed that the antigenic binding pattern (mainly within the 100-200-kDa region) was very similar in patients and controls. Staining intensity, however, appeared to be higher with the leprosy sera than with the control sera. IgM and IgG were found to contribute to the staining pattern: IgM in the 150-200-kDa range, IgG with multiple bands between 25 kDa and 200 kDa. Thus, the presence and levels of serum anti-PNS antibodies in leprosy appear to be unrelated to parameters of disease activity, neuropathy in particular, and do not seem to be critically involved in the pathogenesis of nerve damage.
Antibody Specificity↗
Serum IgA1 and IgM antibodies against Mycobacterium leprae-derived phenolic glycolipid-I: a comparative study in leprosy patients and their contacts.
In order to evaluate the potentials of IgA1 versus IgM as well as of native phenolic glycolipid-I (PGL-I) versus PGL-I-disaccharide coupled to bovine serum albumin (D-BSA) as antigens in the serodiagnosis of leprosy, anti-D-BSA IgA1 and anti-PGL-I IgM were investigated and compared to anti-PGL-I IgA1 in sera from patients and contacts. Anti-D-BSA and anti-PGL-I IgA1 significantly correlate in patients and contacts. The higher IgA1 positivity rates obtained with D-BSA as compared to PGL-I may suggest D-BSA as the favorable antigenic material. In patients but not in contacts anti-PGL-I IgM and IgA1 correlate, IgM predominating over IgA1. In all three antibody systems, the mean values as well as the positivity rates increased from the tuberculoid toward the lepromatous disease pole. Also, the levels of all three antibodies significantly increased with the bacterial index (BI). However, anti-D-BSA (PGL-I) IgA1 appears to be preferable to IgM with respect to sensitivity, i.e., detection of disease activity, in paucibacillary or BI-negative patients. A number of contacts were detected as seropositive with anti-D-BSA and/or anti-PGL-I IgA1 but not with anti-PGL-I IgM. This suggests that IgA1 is a better tool than IgM for the detection of leprosy in its subclinical stage.
Antibodies, Bacterial↗
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.
Antibodies, Bacterial↗
Phytanic acid and very long chain fatty acids in genetic peroxisomal disorders.
1. Phytanic acid, phytanyl-triacylglycerols, and very long chain fatty acids were analysed by gas chromatography or thin-layer chromatography in blood and tissues of patients with different genetic peroxisomal disorders (Refsum's disease, X-linked adrenoleukodystrophy, neonatal adrenoleukodystrophy, Zellweger syndrome). 2. We evaluated these analyses in the detection of patients with Refsum's disease, X-linked adrenoleukodystrophy, neonatal adrenoleukodystrophy, and Zellweger syndrome, and of carriers of X-linked adrenoleukodystrophy. In particular, the analysis of phytanyl-triacylglycerols by thin-layer chromatography proved to be a rapid and reliable method for the detection of patients and the monitoring of their dietary treatment in Refsum's disease. In X-linked adrenoleukodystrophy, carrier detection may depend on very long chain fatty acid analysis in more than one material (e.g. plasma and fibroblasts). 3. Analysis of phytanic acid showed that in patients with multiple impairments of peroxisomal functions (Zellweger syndrome, neonatal adrenoleukodystrophy) phytanic acid levels may be increased not only in serum, but also in the tissue (e.g. brain, adrenals, kidney). 4. Analysis of very long chain fatty acids in cholesterol esters from the brain, adrenals, kidney, and liver of patients with peroxisomal disorders revealed four different types of very long chain fatty acid patterns according to the behaviour of C 26:0 and of other saturated and monounsaturated very long chain fatty acids.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenal Glands↗
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.
Albumins↗
Adrenoleukodystrophy in an adult female. A clinical, morphological, and neurochemical study.
A 43-year-old female with adrenoleukodystrophy (ALD) is described, who developed spastic tetraparesis, suffered grand mal seizures, and became stuporous and demented during the last 5 years of her life. Computed tomography revealed symmetrical hypodense lesions in the peritrigonal regions. Adrenal insufficiency was not evident except for skin pigmentation. The ultrastructure of a rectal biopsy specimen showed inclusions with lamellae and interspersed clefts in macrophages of the submucosal layer. At autopsy, the adrenals were found to contain large foam cells filled with similar inclusions. The brain cortex and the spinal cord were histologically normal. However, cerebral white matter exhibited widespread demyelination which spared only the arcuate fibres. In regions of less severe demyelination scattered inflammatory cells were seen. On electron microscopy, aggregates of typical paired leaflets with distinct intermediate lines were demonstrated in perivascular macrophages. Histochemical study showed these cells to contain free as well as esterified cholesterol. Gas chromatographic analysis of very long chain fatty acids (VLFA) from the demyelinated cerebral white matter showed a marked increase of C26:0 fatty acid in cholesterol esters and above-normal values for C24:0 and C24:1 in gangliosides. It is suggested that the condition was a heterozygote form of X-linked ALD. Patients with neurodegenerative symptoms with or without adrenal insufficiency can easily be screened for X-linked ALD by VLFA analysis in blood or cultured fibroblasts.
Adrenal Glands↗
Very long chain fatty acids in genetic peroxisomal disease fibroblasts: differences between the cerebro-hepato-renal (Zellweger) syndrome and adrenoleukodystrophy variants.
Very long chain fatty acids were investigated by gas chromatography in fibroblasts of patients with genetic peroxisomal diseases (cerebro-hepato-renal (Zellweger) syndrome, childhood adrenoleukodystrophy, adrenomyeloneuropathy, neonatal adrenoleukodystrophy) and of controls. Concentrations of C 26:0 were increased to about the same extent in all disorders investigated. C 26:1 concentrations, on the other hand, were considerably elevated only in the cerebro-hepato-renal syndrome. In all control, adrenoleukodystrophy, and adrenomyeloneuropathy cases the C 22:0 concentration was higher than the respective C 26:0 concentration; the reverse was found in the cerebro-hepato-renal syndrome. These differences seem to reflect different impairment of peroxisomes in the cerebro-hepato-renal syndrome and adrenoleukodystrophy variants, respectively. Additional experiments to characterize C 26:1 by thin layer chromatography, gas chromatography and mass spectrometry revealed the presence of two straight-chain C 26:1 isomers with similar fragmentation patterns.
Abnormalities, Multiple↗
Ganglioside GM1, a molecular target for immunological and toxic attacks: similarity of neuropathological lesions induced by ganglioside-antiserum and cholera toxin.
Ganglioside-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.
Animals↗
Specificity of ganglioside binding to rat macrophages.
The binding specificity of rat alveolar macrophages (AM phi) for sheep erythrocytes (E) coated with gangliosides GM1, GM2, GM3, GD1a, GD1b or GT1b was analyzed in a rosette assay by studying the inhibitory effect of gangliosides, various carbohydrates, IgG, C3b-like C3, and fibronectin in this assay. The uptake of gangliosides by E was calculated from radioactivity measurements using 3H-labeled gangliosides. The different gangliosides were taken up by E at 37 degrees C to a similar extent. Uptake of 3H-labeled GM2 correlated linearly to its concn in the incubation medium. Erythrocytes pretreated with the same molar concn of GM2, GD1a, GD1b or GT1b were bound to AM phi to the same degree reaching a maximum of about 90% rosette forming cells. A mean of 17.8% AM phi-bound GM3-coated E. Treatment of E with asialo-GM2 (GA2) or GM1 did not induce significant rosette formation. A dose-dependent inhibition of rosette formation was observed when AM phi were preincubated at 0 degree C with GM2, GM3, GD1a, GD1b or GT1b, but not with GM1 or GA2 Of the tested carbohydrates, sialyl-lactose had a strong inhibitory effect, while lactose was completely ineffective. N-acetyl-neuraminic acid, N-glycolyl-neuraminic acid and N-acetyl-galactosamine were slightly inhibitory. A series of other carbohydrates including highly negatively charged compounds, as well as fibronectin, IgG or C3b-like C3 did not show significant inhibition. Our data indicate the expression of a receptor on rat AM phi recognizing carbohydrates containing sialic acid at or near the non-reducing terminus.
Animals↗