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Lack of humoral response against Helicobacter pylori peptides homologous to human ZnT8 in Hashimoto’s thyroiditis patientsmore
by Davide Cossu and Speranza Masala
The Helicobacter pylori (HP) reinfection rate seems to be higher in developing countries than in developed ones. An increased seroprevalence of HP has also been reported in patients with type 1 diabetes (T1D) and... more
The Helicobacter pylori (HP) reinfection rate seems to be higher in developing countries than in developed ones. An increased seroprevalence of HP has also been reported in patients with type 1 diabetes (T1D) and Hashimoto's thyroiditis (HT). Mycobacterium avium subsp. paratuberculosis (MAP) has been linked to both T1D and HT. Quite a few lines of evidence indicate that autoantibodies against several epitopes belonging to human zinc transporter 8 (ZnT8) cross-recognize the homologous MAP3865c epitopes in both T1D and HT patients. HP may play a role in HT disease, most likely acting through a molecular mimicry mechanism that targets ZnT8 as reported for MAP and the two autoimmune diseases. An enzyme-linked immunosorbent assay (ELISA) has been developed for the detection of antibodies against several epitopes deriving from HP proteins, which are highly homologous to the immunodominant ZnT8 peptides previously identified: ZnT8178-186 and ZnT8186-194. None of the HP peptides tested were significantly recognized when the humoral responses of 92 HT patients and 91 healthy volunteers were analyzed. These findings do not support a triggering role for HP (through ZnT8 mimicking) in HT. If a molecular mimicry phenomenon is taking place, it involves a different self-antigen. Moreover, the negative outcome of the experiments performed stresses the fact that sharing stretches of sequence homology is relevant, but not enough to trigger an antibody-mediated cross-recognition.
Publication Date: 2015
Publication Name: The Journal of Infection in Developing Countries
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An evaluation of the utility of rep PCR typing compared to the 15 loci discriminatory set of MIRU-VNTR was undertaken. Twenty-nine isolates of Mycobacterium tuberculosis from patients were examined. Genomic DNA was extracted from the... more
An evaluation of the utility of rep PCR typing compared to the 15 loci discriminatory set of MIRU-VNTR was undertaken. Twenty-nine isolates of Mycobacterium tuberculosis from patients were examined. Genomic DNA was extracted from the isolates by standard method. The number of copies of tandem repeats of the 15 MIRU-VNTR loci was determined by PCR amplification and agarose gel electrophoresis of the amplicons. M. tuberculosis outbreak-related strains were distinguished from other isolates. MIRU-VNTR typing identified 4 major clusters of strains. The same isolates clustered together after RFLP typing, but rep-PCR identified only 3 of them. The concordance between RFLP and MIRU-VNTR typing was complete, with the exception of two isolates with identical RFLP patterns that differed in the number of tandem repeat copies at two MIRU-VNTR alleles. A further isolate, even sharing the same RFLP pattern, differed by one repeat from the rest of its cluster. We also tested the use of an automate...
Publication Date: 2010
Publication Name: The new microbiologica
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Proinsulin and MAP3865c homologous epitopes are a target of antibody response in new-onset type 1 diabetes children from continental Italymore
by Davide Cossu and Speranza Masala
Mycobacterium avium subspecies paratuberculosis (MAP) asymptomatic infection is speculated to play a role in type 1 diabetes (T1D) among Sardinian subjects. Data obtained analyzing a pediatric population from mainland Italy lends support... more
Mycobacterium avium subspecies paratuberculosis (MAP) asymptomatic infection is speculated to play a role in type 1 diabetes (T1D) among Sardinian subjects. Data obtained analyzing a pediatric population from mainland Italy lends support to the hypothesis, which envisions MAP as an environmental factor at play in T1D pathogenesis. Aiming to investigate the likelihood of cross-recognition between linear determinants shared by self (proinsulin) and non-self (MAP) proteins, 59 children with new onset T1D and 60 healthy controls (HCs) from continental Italy were enrolled in the study. Serum samples were subjected to indirect enzyme-linked immunosorbent assay (ELISA) for the presence of antibodies (Abs) toward four homologues MAP/proinsulin epitopes. The rate of MAP infection (42.4% in T1D children and 5% in HCs; p < 0.0001) was estimated searching for Abs against MAP specific protein MptD. The homologous MAP2404c70 -85 and proinsulin (PI)46 -61 peptides were recognized by 42.4 and 39% of new-onset T1D children and only in 5% of HCs (AUC = 0.76, AUC = 0.7, p < 0.0001); whereas the prevalence of Abs against MAP 1,4-α-gbp157 -173 and PI64 -80 peptides was 45.7 and 49.1% in new-onset T1D children, respectively, compared with 3.3% of HCs (AUC = 0.74 and p < 0.0001 in both). Pre-incubation of MAP Ab-positive sera with proinsulin peptides was able to block the binding to the correspondent MAP epitopes, thus showing that Abs against these homologous peptides are cross-reactive. MAP/Proinsulin Ab mediated cross-recognition, most likely via molecular mimicry, maybe a factor in accelerating and/or initiating T1D in MAP-infected children. Indeed, it is known that anti-proinsulin and anti-Insulin autoantibodies are the earliest to appear.
Publication Date: 2015
Publication Name: Pediatric Diabetes
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by Speranza Masala and Gianni Pes
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Publication Date: 2014
Publication Name: Multiple Sclerosis Journal
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Publication Date: 2014
Publication Name: PLoS ONE
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Publication Date: 2014
Research Interests: Macrophages, Biological Chemistry, Gene Silencing, Western blotting, Signal Transduction, and 22 moreBiological Sciences, Toll Like Receptors, Cell line, Mycobacterium tuberculosis, Mice, Animals, Biological, NF-kappa B, Phosphorylation, Plasmids, Phenotype, Immunoprecipitation, Clinical Sciences, CHEMICAL SCIENCES, Lipopolysaccharides, Transfection, Protein Binding, Mannose, Enzyme Linked Immunosorbent Assay, Gene Expression Regulation, Interleukin, and Oligosaccharides
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Bacillus Calmette-Guérin (BCG) and Mycobacterium avium subspecies paratuberculosis (MAP) have been associated with multiple sclerosis (MS). Clinical data indicates that BCG vaccination exerts anti-inflammatory effects in MS; conversely,... more
Bacillus Calmette-Guérin (BCG) and Mycobacterium avium subspecies paratuberculosis (MAP) have been associated with multiple sclerosis (MS). Clinical data indicates that BCG vaccination exerts anti-inflammatory effects in MS; conversely, MAP is thought to be one of the possible infectious factors responsible of MS through a molecular mimicry mechanism. A peptide-based indirect ELISA was used to detect antibodies against the encephalitogenic myelin oligodendrocyte glycoprotein (MOG)35-55 epitope, and two mycobacterial peptides sharing sequence homology with the latter: MAP_2619c352-361/BCG_1224355-364 and BCG_3329c64-74. Among 40 MS patients and 39 healthy volunteers included in the study, only MOG35-55 was capable of inducing a significantly higher humoral response in MS subjects compared to controls. Indeed, 11 out of 40 MS subjects (27.5%) and only 2 out of 39 controls (5%) were antibody-positive for MOG35-55 (p=0.01, AUC=0.65). These findings strengthen the importance of MOG35-55 in MS pathogenesis. The MAP and BCG MOG-homologues epitopes investigated were not recognized in MS patients. Overall, the results allow us concluding that sharing homology of linear epitopes is necessary but not sufficient to induce antibody-mediated cross-reactivity.
Publication Date: 2014
Publication Name: Journal of the Neurological Sciences
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Publication Date: 1995
Publication Name: Preparative Biochemistry
Research Interests: Technology, Phytochemistry, Kinetics, Heat Treatment, Biological Sciences, and 24 moreLaTeX, Temperature, Plants, Hevea brasiliensis, Spectrophotometry, Electron Transport, Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis, Affinity chromatography, Ion Exchange Chromatography, Rubber, Enzyme, CHEMICAL SCIENCES, Soybeans, Thermal Stability, Substrate Specificity, Enzyme activity, Molecular Mass, Hevea, Quinone Reductase, Molecular weight, NAD, Glycine max, Hydrogen-Ion Concentration, and Yield potential
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Publication Date: 2013
Publication Name: PLoS ONE
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Publication Date: 2011
Publication Name: PLoS ONE
Research Interests: Genetics, Multiple sclerosis, Multidisciplinary, T cell receptor, Italy, and 16 moreHumans, Female, Male, Polymerase Chain Reaction, DNA fingerprinting, PLoS one, Middle Aged, Molecular cloning, Genotype, Adult, Molecular Mimicry, Association Mapping, Amino Acid Sequence, Enzyme Linked Immunosorbent Assay, Western Mediterranean, and Paratuberculosis
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Publication Date: 2011
Publication Name: PLoS ONE
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Publication Date: 2013
Publication Name: Placenta
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Publication Date: 2013
Publication Name: Nutrition, Metabolism and Cardiovascular Diseases
Research Interests: Demography, Food Science, Epidemiology, Nutrition, Life Style, and 18 morePhysical Activity, Food and Nutrition, Italy, Longevity, Humans, Sardinia, Male, Lifestyle, Nutritional Status, Risk factors, Prevalence, Risk Factors, Indexation, Occupations, Environment, Logistic Models, Motor activity, and Socioeconomic Factors
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Are Mycobacterium avium subsp. paratuberculosis and Epstein-Barr virus triggers of multiple sclerosis in Sardinia?more
by Davide Cossu and Speranza Masala
Publication Date: 2012
Publication Name: Multiple Sclerosis Journal
Research Interests: Multiple sclerosis, Risk assessment, Italy, Humans, Female, and 16 moreMale, Polymerase Chain Reaction, Risk factors, Clinical Sciences, Prevalence, Middle Aged, Adult, Odds ratio, Chi Square Distribution, Risk Factors, Risk Assessment, Neurosciences, Enzyme Linked Immunosorbent Assay, Logistic Models, Case Control Studies, and Paratuberculosis
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Anti Mycobacterium avium subsp. paratuberculosis heat shock protein 70 antibodies in the sera of Sardinian patients with multiple sclerosismore
by Davide Cossu and Speranza Masala
Publication Date: 2013
Publication Name: Journal of the Neurological Sciences
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Publication Date: 2013
Publication Name: Journal of Neuroimmunology
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Publication Date: 2014
Publication Name: Journal of Neuroimmunology
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Publication Date: 2010
Publication Name: Journal of Clinical Microbiology
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Publication Date: 2009
Publication Name: Journal of Clinical Microbiology
Research Interests: Polymorphism, Adolescent, Comparative Study, Clinical Microbiology, Biological Sciences, and 19 moreCanada, Tuberculosis, Humans, Child, Mycobacterium tuberculosis, Country of Origin, Female, Clinical, Male, Cluster Analysis, Young Adult, DNA fingerprinting, Infant, Ethnic Groups, Aged, Middle Aged, Genotype, Adult, and Human Disease
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Sardinian Type 1 diabetes patients, Transthyretin and Mycobacterium avium subspecies paratuberculosis infectionmore
by Davide Cossu and Speranza Masala
Publication Date: 2012
Publication Name: Gut Pathogens
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Publication Date: 2013
Publication Name: Future Microbiology
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Publication Date: 2006
Publication Name: Applied and Environmental Microbiology
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Publication Date: 2013
Publication Name: Acta Ophthalmologica
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Recognition of zinc transporter 8 and MAP3865c homologous epitopes by new-onset type 1 diabetes children from continental Italymore
by Davide Cossu and Speranza Masala
Publication Date: 2014
Publication Name: Acta Diabetologica
Research Interests: Adolescent, Multidisciplinary, Italy, Humans, Child, and 18 moreFemale, Male, Young Adult, Monoclonal Antibodies, Peptides, PLoS one, Clinical Sciences, Middle Aged, Epithelial cells, Adult, Type 2 Diabetes Mellitus, Epitopes, Enzyme Linked Immunosorbent Assay, Area Under Curve, Autoantibodies, immunoglobulin G, Case Control Studies, and Cohort Studies
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Publication Date: 2014
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The etiology of type 1 diabetes mellitus (T1DM) is still unknown; numerous studies are performed to unravel the environmental factors involved in triggering the disease. SLC11A1 is a membrane transporter that is expressed in late... more
The etiology of type 1 diabetes mellitus (T1DM) is still unknown; numerous studies are performed to unravel the environmental factors involved in triggering the disease. SLC11A1 is a membrane transporter that is expressed in late endosomes of antigen presenting cells involved in the immunopathogenic events leading to T1DM. Mycobacterium avium subsp. paratuberculosis (MAP) has been reported to be a possible trigger in the development of T1DM. Fifty nine T1DM patients and 79 healthy controls were genotyped for 9 polymorphisms of SLC11A1 gene, and screened for the presence of MAP by PCR. Differences in genotype frequency were evaluated for both T1DM patients and controls. We found a polymorphism in the SLC11A1 gene (274C/T) associated to type 1 diabetic patients and not to controls. The presence of MAP DNA was also significantly associated with T1DM patients and not with controls. The 274C/T SCL11A1 polymorphism was found to be associated with T1DM as well as the presence of MAP DNA in...