i(3)so3-galactosylceramide and Chronic-Disease

Topics: Antibody Specificity; Autoantibodies; Autoantigens; Autoimmune Diseases; Brain; Carbohydrate Sequence; CD57 Antigens; Chronic Disease; G(M1) Ganglioside; Gangliosides; Globosides; Glycolipids; Guillain-Barre Syndrome; Humans; Immunoglobulin M; Molecular Sequence Data; Motor Neuron Disease; Myelin Sheath; Paraproteinemias; Peripheral Nervous System; Polyradiculoneuropathy; Sulfoglycosphingolipids

Increasing evidence suggests that in Chagas' disease chronic-phase pathology is autoimmune in nature. There are at least two nonexclusive explanations for the generation of autoimmunity in Chagas disease: a) infection with the parasite perturbs immunoregulation, leading to loss of tolerance for self-antigens; b) immune recognition of T. cruzi antigens is crossreactive with selected mammalian antigens, leading to autoimmunity (molecular mimicry). Through this latter mechanism, T. cruzi antigens that share epitopes with mammalian nervous tissue may drive autoreactive B- or T-cell clones to expand and cause autoimmune lesions in chronic chagasic patients. Several different antigens sharing this characteristic have been studied, as for example the 160-kDa flagellum-associated surface protein (Fl-160), which has a nervous tissue crossreactive epitope composed by twelve amino acids. Additionally, it has been demonstrated that a trypomastigote stage-specific 85kDa surface glycoprotein (Gp85) has terminal galactosyl(alpha 1-3)galactose terminal residues, which are reactive with chronic chagasic sera. Common glycolipid antigens have also been reported, as for example galactocerebroside, sulfogalactocerebroside and sulfoglucuronylcerebroside, all of them specifically present at high concentrations in mammalian nervous system and in T. cruzi trypomastigotes. Chronic chagasic patients produce elevated levels of antibodies against these three glycolipid antigens. They also do against terminal galactosyl(alpha 1-3)galactose residues present on several acid and neutral glycolipids common either to nervous system or parasite. These antibodies are powerful lytic for circulating T. cruzi trypomastigotes. Another common strongly immunogenic residues are galactosyl(alpha 1-2)galactose, galactosyl(alpha 1-6)galactose and galactofuranosyl(beta 1-3)mannose residues present on several glycoinositolphospholipids (GIPL), against which chronic chagasic patients have elevated levels of specific antibodies. In brief, very specific host-parasite relationships existing only in Chagas' disease may explain the particular peripheral nervous tissue damage seen in acute or chronic stages of this disease. This specificity could depend either on invasion of autonomic ganglia by T. cruzi trypomastigotes and modification of nervous cell surface structures by some of the several mechanisms of acquired molecular mimicry.

Topics: Amino Acid Sequence; Animals; Antibodies, Protozoan; Antigens, Protozoan; Autoantibodies; Autoantigens; Autoimmune Diseases; Carbohydrate Sequence; Chagas Disease; Chronic Disease; Cross Reactions; Galactose; Galactosylceramides; Glucose; Glycosylphosphatidylinositols; Molecular Sequence Data; Nerve Tissue Proteins; Protozoan Proteins; Sulfoglycosphingolipids; Trypanosoma cruzi

Despite its importance as the leading cause of vascular dementia, the primary pathogenic mechanisms in subcortical ischemic vascular dementia (SIVD) have remained elusive. Because of the lack of approved therapeutic agents for SIVD, there is a pressing need to identify novel therapeutic targets. Comparative lipidomic analyses of SIVD and mixed dementia (i.e., SIVD and Alzheimer's disease, MixD) may also confer new insights pertaining to the possible interaction between neurodegenerative and vascular mechanisms in the pathogenesis of dementia. Liquid chromatography coupled to mass spectrometry was used to comprehensively analyze the lipidomes of white and gray matter from the temporal cortex of nondemented controls, SIVD, and MixD subjects. Detailed molecular profiles highlighted the pathologic relevance of gray matter sphingolipid fatty acyl chain heterogeneity in dementia. In addition, the levels of sulfatides and lysobisphosphatidic acids were progressively increased in the temporal cortex gray matter from control to SIVD to MixD. White matter phospholipid profiles indicated possible adaptive mechanisms (i.e., increased unsaturation) to chronic ischemia in SIVD and elevated membrane degradation in MixD.

Topics: Aged; Aged, 80 and over; Brain Ischemia; Chromatography, Liquid; Chronic Disease; Dementia, Vascular; Female; Gray Matter; Humans; Lysophospholipids; Male; Mass Spectrometry; Monoglycerides; Phospholipids; Sphingolipids; Sulfoglycosphingolipids; Temporal Lobe; White Matter

Sulfatides highly expressed in the normal gastric mucosa play important roles in gastric mucosal protection. However, it is unknown whether the sulfatides expression changes in chronic gastritis.. Sulfatides expression levels were examined with immunohistochemical staining in 77 specimens obtained from resected human stomachs, followed by the measurement of optical density of the staining under digital microscopy. For mRNA expression analysis of GalCer (galactosylceramide)-sulfotransferase and arylsulfatase A using a quantitative real time reverse transcription-polymerase chain reaction, 64 biopsy specimens were endoscopically taken from the gastric corpus of out patients. Mucosal changes were scored under microscopic observations according to the updated Sydney System classification.. The sulfatides expression decreased along with the progression of mucosal atrophy and lymphocytes infiltration, and was barely observed in intestinal metaplasia. The mRNA expression of GalCer-sulfotransferase, a biosynthetic enzyme for sulfatides, also decreased along with the progression of mucosal atrophy and lymphocytes infiltration. In contrast, mRNA expression of arylsulfatase A, which degrades sulfatides, was not altered.. Expression of sulfatides and GalCer-sulfotransferase in the gastric mucosa of chronic gastritis is selectively reduced according to the mucosal atrophy and inflammation. Decreased expression of sulfatides may attribute to the deterioration of mucosal protection in chronic gastritis.

Topics: Atrophy; Biopsy; Cerebroside-Sulfatase; Chronic Disease; Down-Regulation; Gastric Mucosa; Gastritis; Humans; Immunohistochemistry; Inflammation; Lymphocytes; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sulfoglycosphingolipids; Sulfotransferases

Earlier studies in Trypanosoma cruzi-infected rats revealed an increased antibody activity against sulfatide, a specific constituent of both myelin sheaths of peripheral nerves and T. cruzi epimastigotes. To investigate further the characteristics of such anti-sulfatide antibodies, we analyzed their IgG isotypes as well as their ability to bind to homologous neural host structures. Antisulfatide IgG-enriched fractions were obtained from rats acutely infected with T. cruzi. Immunoglobulin isotypes were determined by an enzyme-linked immunosorbent assay (ELISA) method to show that IgG2a and, more significantly, IgG2b were the predominant isotypes of antisulfatide autoantibodies. Further immunofluorescence studies carried out in coronal sections of the rat forebrain revealed, in turn, that antisulfatide antibodies were capable of reacting with homologous neural tissues. Specific binding of these rat autoantibodies to sulfocerebroside on cell surfaces in vivo may in theory play some detrimental role, given the reported ability of rat IgG2b to fix complement or to mediate antibody-dependent cell-mediated cytotoxicity reactions.

Topics: Acute Disease; Animals; Antibody Specificity; Autoantibodies; Chagas Disease; Chronic Disease; Corpus Callosum; Female; Immunoglobulin G; Immunoglobulin Isotypes; Male; Prosencephalon; Rats; Rats, Inbred Strains; Sulfoglycosphingolipids

A specific treatment for Chagas' disease has not yet been discovered, even though the condition is endemic in large parts of the Region of the Americas. Earlier studies have addressed the possibility that the sulfatide galactocerebroside in Trypanosoma cruzi behaves as an immunogen involved in the production of the high antisulfatide antibody levels found in patients with chronic infestation with the parasite. This may be an important factor in the pathogenesis of the cardiac symptoms and peripheral neuropathy seen in Chagas' disease, which is the most important cause of myocarditis in Central and South America and the second most important cause of heart failure in several of the countries located in these subregions. The present study was conducted in order to ascertain whether patients with Chagas' disease and other patients not afflicted with the ailment differ insofar as the presence of antibodies against sulfatide is concerned, and it describes antisulfatide antibody levels in 124 hospital patients (74 men and 50 women) between the ages of 15 and 94 who were in the cardiology unit of Vargas Hospital in Caracas from 1 July to 30 June 1995. Antisulfatide antibody titers were determined by means of enzyme-linked immunosorbent assays (ELISA), and the antigen employed was sulfatide cerebroside obtained from bovine brain tissue. Of the 124 patients under study, 39 (31.5%) suffered from Chagas' disease and had antisulfatide antibody levels higher than those detected in patients without Chagas (P = 0.0298) and in 28 seemingly healthy controls (P = 0.0035). Serum levels of antisulfatide antibodies in patients with other forms of heart disease were also compared with those seen in the control group, and significantly higher levels were found in patients with acute ischemic heart disease (P = 0.0049), rheumatic valvular heart disease (P = 0.0075), chronic ischemic heart disease (P = 0.0464) and bradiarrythmias (P = 0.0157), and significantly lower ones in subjects with hypertensive heart disease (P = 0.0367). These antibody levels showed no correlation with clinical or paraclinical variables indicative of the degree of cardiac compromise. Our results support the notion that antibodies against sulfatide may play a role in the pathogenesis of Chagas' cardiomyopathy and other forms of heart disease and should be further studied in an effort to determine their potential role in these processes.

Topics: Animals; Antibodies, Protozoan; Cattle; Chagas Cardiomyopathy; Chronic Disease; Female; Heart Diseases; Humans; Male; Sulfoglycosphingolipids; Trypanosoma cruzi

The clinical and electrophysiological features were prospectively studied of 75 patients (46 men and 29 women) with chronic polyneuropathy presenting in middle or old age in whom a diagnosis could not be made even after extensive evaluation and a follow up of six months. The mean age at the onset of symptoms was 56.5 years. The clinical features of chronic idiopathic polyneuropathy are heterogeneous. On clinical grounds 44 patients had a sensorimotor, 29 patients a sensory, and two patients a motor polyneuropathy. The overall clinical course in chronic idiopathic polyneuropathy was slowly progressive. None of the patients became severely disabled. Electrophysiological and nerve biopsy studies were compatible with an axonal polyneuropathy. Antibodies against myelin associated glycoprotein, gangliosides, and sulphatides were assessed in 70 patients and found to be negative.

Topics: Age of Onset; Autoantibodies; Chronic Disease; Electromyography; Female; G(M1) Ganglioside; Humans; Male; Middle Aged; Myelin Proteins; Myelin-Associated Glycoprotein; Neural Conduction; Peripheral Nerves; Peripheral Nervous System Diseases; Prospective Studies; Sulfoglycosphingolipids

Sera from eight of 25 patients with chronic sensory neuropathy had high titers of antibodies to sulfatide and chondroitin sulfate C or both. Preclearing of patients' sera with either sulfatide or chondroitin sulfate C revealed that in four patients the antisulfatide antibodies crossreacted with chondroitin sulfate C. By indirect immunohistochemistry sera reactive to sulfatide only had a different staining pattern from those reactive to both sulfatide and chondroitin sulfate C. By direct immunohistochemistry we found immunoglobulins bound to nerve fibers only in patients with serum antibodies against both sulfatide and chondroitin sulfate C. Our study provides evidence that antibodies to sulfatide and to chondroitin sulfate C differ in their fine specificity and are present in 30% of patients with chronic sensory neuropathy.

Topics: Adult; Aged; Antibodies; Chondroitin Sulfates; Chronic Disease; Female; Humans; Immunohistochemistry; Male; Middle Aged; Neurons, Afferent; Peripheral Nervous System Diseases; Sulfoglycosphingolipids

A natural anti-sulphatide antibody was found to be present in the serum of every normal individual studied. The reactivity of the antibody was assessed by its interaction with galactosylceramide-I3-sulphate. Antigen-antibody binding was strongly blocked by 1 mM heparin, dextran sulphate and chondroitin sulphate A, and by 5 mM chondroitin sulphate B. Antibodies avidly absorb to rabbit erythrocytes, but discretely to rat erythrocytes, suggesting that they are different from galactocerebroside antibodies. Elevated levels of sulphatide antibodies were present in all of 102 chronic Trypanosoma cruzi-infected patients studied, but not in other patients having cutaneous or visceral leishmaniasis, T. rangeli infection or several other protozoal, helminthic or mycotic infections. Interestingly, 100% of 40 dilated cardiomyopathy patients also have elevated levels of sulphatide antibodies. As T. cruzi is rich in galactocerebroside sulphate, it is proposed that in chagasic patients this glycolipid could act as an immunogen, inducing elevated titres of sulphatide antibodies, which could be important in the pathogenesis of cardiac or peripheral nerve symptoms.

Topics: Adolescent; Adult; Aged; Antibody Specificity; Autoantibodies; Cardiomyopathy, Dilated; Chagas Disease; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Erythrocytes; Female; Helminthiasis; Humans; Immunoglobulins; Male; Middle Aged; Mycoses; Protozoan Infections; Sulfoglycosphingolipids

Topics: Acute Disease; Animals; Brain; Cerebral Cortex; Cerebrosides; Cholesterol; Chronic Disease; Glucuronidase; Humans; Hydrolases; Lipid Metabolism; Lysosomes; Multiple Sclerosis; Myelin Sheath; Nerve Tissue Proteins; Peptide Hydrolases; Phosphatidylcholines; Phosphatidylethanolamines; Phospholipids; Rats; Sulfatases; Sulfoglycosphingolipids

Chronic triethyl tin intoxication was induced in young adult rats by oral feeding of triethyl tin sulfate. Progressively severe brain edema developed during the 3-month experimental period. The yield of myelin from the brains of the experimental animals decreased to almost half normal per brain, but the isolated myelin appeared morphologically normal. The analysis of whole brain showed corresponding decreases in proteolipid protein and total lipid, particularly galactolipids. The proportions of the major constituents of isolated myelin (chloroform-methanol-insoluble residue, proteolipid protein, and total lipid) were unchanged despite the low yield. However, the proportion of cholesterol increased from 16 to 21% dry weight, and that of total galactolipid decreased from 21 to 15%, as the yield of myelin decreased. This decrease of total galactolipid was mainly due to the decrease in cerebroside. Total phospholipid remained constant initially but showed a slight decrease toward the end of the experiment, due mostly to decreased ethanolamine phospholipid. There was no preferential loss or preservation of phosphatidalethanolamine. The fatty acid composition of sulfatide showed statistically significant shifts to less long-chain fatty acids and less monoenoic acids, but cerebroside and sphingomyelin did not show significant changes in the fatty acid composition. There was no increase in esterified cholesterol. These findings generally support our hypothesis of nonspecific chemical abnormalities of the myelin sheath undergoing secondary degeneration. In an acute experiment, a single intraperitoneal injection of triethyl tin sulfate produced acute and transient brain edema. There were slight decreases in the yield of myelin, but no detectable changes in the chemical composition.

Topics: Administration, Oral; Animals; Brain; Brain Chemistry; Brain Edema; Cholesterol; Chronic Disease; Depression, Chemical; Fatty Acids; Glycolipids; Injections, Intraperitoneal; Lipids; Lipoproteins; Metabolism; Microscopy, Electron; Myelin Sheath; Organ Size; Organometallic Compounds; Phosphatidylethanolamines; Phospholipids; Rats; Stimulation, Chemical; Sulfoglycosphingolipids; Sulfuric Acids; Tin