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Manfred F Rajewsky - One of the best experts on this subject based on the ideXlab platform.

  • affinity purification and cdna cloning of rat neural differentiation and tumor Cell surface antigen gp130rb13 6 reveals relationship to human and murine pc 1
    Journal of Biological Chemistry, 1995
    Co-Authors: Helmut Deissler, Friedrich Lottspeich, Manfred F Rajewsky
    Abstract:

    Abstract Monoclonal antibody RB13-6 recognizes a subset of rat brain glial precursor Cells that are highly susceptible to malignant conversion by the carcinogen N-ethyl- N-nitrosourea. The corresponding Cell surface antigen was identified as a Membrane glycoProtein (gp130RB13-6) and purified by immunoaffinity chromatography from the tumorigenic neuroectodermal rat Cell line BT4Ca. Sequencing of 5 endoProteinase-generated peptides of the purified antigen permitted the specific amplification of a cDNA fragment by reverse transcription-polymerase chain reaction and subsequent isolation of the complete coding sequence from a fetal rat brain cDNA library. The derived amino acid sequence indicates that the RB13-6 antigen is related to the human and murine plasma Cell Membrane Protein PC-1, a nucleotide pyrophosphatase/alkaline phosphodiesterase and ectoProtein kinase. Similarly, purified gp130RB13-6possesses 5′-nucleotidase activity that can be inhibited with EDTA. Different from PC-1, gp130RB13-6isolated from BT4Ca Cells is not a disulfide-linked dimer and contains an RGD-tripeptide sequence which, together with other structural features, suggests a possible function in Cell adhesion and its subversion in malignant phenotypes.

  • affinity purification and cdna cloning of rat neural differentiation and tumor Cell surface antigen gp130rb13 6 reveals relationship to human and murine pc 1
    Journal of Biological Chemistry, 1995
    Co-Authors: Helmut Deissler, Friedrich Lottspeich, Manfred F Rajewsky
    Abstract:

    Abstract Monoclonal antibody RB13-6 recognizes a subset of rat brain glial precursor Cells that are highly susceptible to malignant conversion by the carcinogen N-ethyl- N-nitrosourea. The corresponding Cell surface antigen was identified as a Membrane glycoProtein (gp130RB13-6) and purified by immunoaffinity chromatography from the tumorigenic neuroectodermal rat Cell line BT4Ca. Sequencing of 5 endoProteinase-generated peptides of the purified antigen permitted the specific amplification of a cDNA fragment by reverse transcription-polymerase chain reaction and subsequent isolation of the complete coding sequence from a fetal rat brain cDNA library. The derived amino acid sequence indicates that the RB13-6 antigen is related to the human and murine plasma Cell Membrane Protein PC-1, a nucleotide pyrophosphatase/alkaline phosphodiesterase and ectoProtein kinase. Similarly, purified gp130RB13-6possesses 5′-nucleotidase activity that can be inhibited with EDTA. Different from PC-1, gp130RB13-6isolated from BT4Ca Cells is not a disulfide-linked dimer and contains an RGD-tripeptide sequence which, together with other structural features, suggests a possible function in Cell adhesion and its subversion in malignant phenotypes.

Speranza Masala - One of the best experts on this subject based on the ideXlab platform.

  • detection of serum antibodies cross reacting with mycobacterium avium subspecies paratuberculosis and beta Cell antigen zinc transporter 8 homologous peptides in patients with high risk proliferative diabetic retinopathy
    PLOS ONE, 2014
    Co-Authors: Antonio Daniele Pinna, Speranza Masala, Francesco Blasetti, Irene Maiore, Davide Cossu, Daniela Paccagnini, Giuseppe Mameli, Leonardo Antonio Sechi
    Abstract:

    Purpose : MAP3865c, a Mycobacterium avium subspecies paratuberculosis (MAP) Cell Membrane Protein, has a relevant sequence homology with zinc transporter 8 (ZnT8), a beta-Cell Membrane Protein involved in Zn++ transportation. Recently, antibodies recognizing MAP3865c epitopes have been shown to cross-react with ZnT8 in type 1 diabetes patients. The purpose of this study was to detect antibodies against MAP3865c peptides in patients with high-risk proliferative diabetic retinopathy and speculate on whether they may somehow be involved in the pathogenesis of this severe retinal disorder. Methods : Blood samples were obtained from 62 type 1 and 80 type 2 diabetes patients with high-risk proliferative diabetic retinopathy and 81 healthy controls. Antibodies against 6 highly immunogenic MAP3865c peptides were detected by indirect ELISA. Results : Type 1 diabetes patients had significantly higher rates of positive antibodies than controls. Conversely, no statistically significant differences were found between type 2 diabetes patients and controls. After categorization of type 1 diabetes patients into two groups, one with positive, the other with negative antibodies, we found that they had similar mean visual acuity (∼0.6) and identical rates of vitreous hemorrhage (28.6%). Conversely, Hashimoto's thyroiditis prevalence was 4/13 (30.7%) in the positive antibody group and 1/49 (2%) in the negative antibody group, a statistically significant difference ( P = 0.016). Conclusions : This study confirmed that type 1 diabetes patients have significantly higher rates of positive antibodies against MAP/ZnT8 peptides, but failed to find a correlation between the presence of these antibodies and the severity degree of high-risk proliferative diabetic retinopathy. The significantly higher prevalence of Hashimoto's disease among type 1 diabetes patients with positive antibodies might suggest a possible common environmental trigger for these conditions.

  • detection of antibodies against homologous mycobacterium avium subspecies paratuberculosis and beta Cell antigen zinc transporter 8 epitopes in sardinian type 1 diabetic patients with proliferative diabetic retinopathy
    Acta Ophthalmologica, 2013
    Co-Authors: Antonio Pinna, Speranza Masala, Francesco Blasetti, Irene Maiore, Davide Cossu, Daniela Paccagnini, E Brundu, La Sechi
    Abstract:

    Purpose Diabetic retinopathy (DR) is the leading cause of new cases of blindness in developed countries. ZnT8, a beta-Cell Membrane Protein involved in Zn++ transportation, may act as a major autoantigen in Type 1 Diabetes (T1D). Dysregulation in Zn++ homeostasis has been implicated in the pathogenesis of ischemia in DR. Mycobacterium avium subspecies paratuberculosis (MAP) causes an asymptomatic human infection transmitted from dairy herds through food contamination. MAP3865c, a MAP Cell Membrane Protein, has been shown to display a relevant sequence homology with ZnT8. Moreover, antibodies recognizing MAP3865c epitopes have been found to cross-react with ZnT8 in T1D patients. The purpose of this study was to detect serum antibodies against 6 highly immunogenic MAP3865c epitopes in T1D patients with proliferative diabetic retinopathy (PDR) and in healthy controls (HCs). Methods Blood samples were obtained from 23 T1D patients with PDR and 39 HCs. Antibodies against 2 trans-Membrane (MAP3865c125–133 MAP3865c133–141) and 4 C terminal (MAP3865c246–252, MAP3865c256–262, MAP3865c261–267 and MAP3865c281–287) peptides were detected by indirect ELISA. Fisher’s exact test and ROC curves were used to assess results. Results Antibodies against MAP3865c peptides were found in 6 out of 23 (26%) T1D patients with PDR and 2 out of 39 (5%) HCs, a statistically significant difference (p=0.04). Conclusion Results suggest that serum antibodies against MAP3865c peptides may play a role in the pathogenesis of PDR in T1D patients.Further larger studies are necessary to confirm these preliminary data.

Francesco Blasetti - One of the best experts on this subject based on the ideXlab platform.

  • detection of serum antibodies cross reacting with mycobacterium avium subspecies paratuberculosis and beta Cell antigen zinc transporter 8 homologous peptides in patients with high risk proliferative diabetic retinopathy
    PLOS ONE, 2014
    Co-Authors: Antonio Daniele Pinna, Speranza Masala, Francesco Blasetti, Irene Maiore, Davide Cossu, Daniela Paccagnini, Giuseppe Mameli, Leonardo Antonio Sechi
    Abstract:

    Purpose : MAP3865c, a Mycobacterium avium subspecies paratuberculosis (MAP) Cell Membrane Protein, has a relevant sequence homology with zinc transporter 8 (ZnT8), a beta-Cell Membrane Protein involved in Zn++ transportation. Recently, antibodies recognizing MAP3865c epitopes have been shown to cross-react with ZnT8 in type 1 diabetes patients. The purpose of this study was to detect antibodies against MAP3865c peptides in patients with high-risk proliferative diabetic retinopathy and speculate on whether they may somehow be involved in the pathogenesis of this severe retinal disorder. Methods : Blood samples were obtained from 62 type 1 and 80 type 2 diabetes patients with high-risk proliferative diabetic retinopathy and 81 healthy controls. Antibodies against 6 highly immunogenic MAP3865c peptides were detected by indirect ELISA. Results : Type 1 diabetes patients had significantly higher rates of positive antibodies than controls. Conversely, no statistically significant differences were found between type 2 diabetes patients and controls. After categorization of type 1 diabetes patients into two groups, one with positive, the other with negative antibodies, we found that they had similar mean visual acuity (∼0.6) and identical rates of vitreous hemorrhage (28.6%). Conversely, Hashimoto's thyroiditis prevalence was 4/13 (30.7%) in the positive antibody group and 1/49 (2%) in the negative antibody group, a statistically significant difference ( P = 0.016). Conclusions : This study confirmed that type 1 diabetes patients have significantly higher rates of positive antibodies against MAP/ZnT8 peptides, but failed to find a correlation between the presence of these antibodies and the severity degree of high-risk proliferative diabetic retinopathy. The significantly higher prevalence of Hashimoto's disease among type 1 diabetes patients with positive antibodies might suggest a possible common environmental trigger for these conditions.

  • detection of antibodies against homologous mycobacterium avium subspecies paratuberculosis and beta Cell antigen zinc transporter 8 epitopes in sardinian type 1 diabetic patients with proliferative diabetic retinopathy
    Acta Ophthalmologica, 2013
    Co-Authors: Antonio Pinna, Speranza Masala, Francesco Blasetti, Irene Maiore, Davide Cossu, Daniela Paccagnini, E Brundu, La Sechi
    Abstract:

    Purpose Diabetic retinopathy (DR) is the leading cause of new cases of blindness in developed countries. ZnT8, a beta-Cell Membrane Protein involved in Zn++ transportation, may act as a major autoantigen in Type 1 Diabetes (T1D). Dysregulation in Zn++ homeostasis has been implicated in the pathogenesis of ischemia in DR. Mycobacterium avium subspecies paratuberculosis (MAP) causes an asymptomatic human infection transmitted from dairy herds through food contamination. MAP3865c, a MAP Cell Membrane Protein, has been shown to display a relevant sequence homology with ZnT8. Moreover, antibodies recognizing MAP3865c epitopes have been found to cross-react with ZnT8 in T1D patients. The purpose of this study was to detect serum antibodies against 6 highly immunogenic MAP3865c epitopes in T1D patients with proliferative diabetic retinopathy (PDR) and in healthy controls (HCs). Methods Blood samples were obtained from 23 T1D patients with PDR and 39 HCs. Antibodies against 2 trans-Membrane (MAP3865c125–133 MAP3865c133–141) and 4 C terminal (MAP3865c246–252, MAP3865c256–262, MAP3865c261–267 and MAP3865c281–287) peptides were detected by indirect ELISA. Fisher’s exact test and ROC curves were used to assess results. Results Antibodies against MAP3865c peptides were found in 6 out of 23 (26%) T1D patients with PDR and 2 out of 39 (5%) HCs, a statistically significant difference (p=0.04). Conclusion Results suggest that serum antibodies against MAP3865c peptides may play a role in the pathogenesis of PDR in T1D patients.Further larger studies are necessary to confirm these preliminary data.

Irene Maiore - One of the best experts on this subject based on the ideXlab platform.

  • detection of serum antibodies cross reacting with mycobacterium avium subspecies paratuberculosis and beta Cell antigen zinc transporter 8 homologous peptides in patients with high risk proliferative diabetic retinopathy
    PLOS ONE, 2014
    Co-Authors: Antonio Daniele Pinna, Speranza Masala, Francesco Blasetti, Irene Maiore, Davide Cossu, Daniela Paccagnini, Giuseppe Mameli, Leonardo Antonio Sechi
    Abstract:

    Purpose : MAP3865c, a Mycobacterium avium subspecies paratuberculosis (MAP) Cell Membrane Protein, has a relevant sequence homology with zinc transporter 8 (ZnT8), a beta-Cell Membrane Protein involved in Zn++ transportation. Recently, antibodies recognizing MAP3865c epitopes have been shown to cross-react with ZnT8 in type 1 diabetes patients. The purpose of this study was to detect antibodies against MAP3865c peptides in patients with high-risk proliferative diabetic retinopathy and speculate on whether they may somehow be involved in the pathogenesis of this severe retinal disorder. Methods : Blood samples were obtained from 62 type 1 and 80 type 2 diabetes patients with high-risk proliferative diabetic retinopathy and 81 healthy controls. Antibodies against 6 highly immunogenic MAP3865c peptides were detected by indirect ELISA. Results : Type 1 diabetes patients had significantly higher rates of positive antibodies than controls. Conversely, no statistically significant differences were found between type 2 diabetes patients and controls. After categorization of type 1 diabetes patients into two groups, one with positive, the other with negative antibodies, we found that they had similar mean visual acuity (∼0.6) and identical rates of vitreous hemorrhage (28.6%). Conversely, Hashimoto's thyroiditis prevalence was 4/13 (30.7%) in the positive antibody group and 1/49 (2%) in the negative antibody group, a statistically significant difference ( P = 0.016). Conclusions : This study confirmed that type 1 diabetes patients have significantly higher rates of positive antibodies against MAP/ZnT8 peptides, but failed to find a correlation between the presence of these antibodies and the severity degree of high-risk proliferative diabetic retinopathy. The significantly higher prevalence of Hashimoto's disease among type 1 diabetes patients with positive antibodies might suggest a possible common environmental trigger for these conditions.

  • detection of antibodies against homologous mycobacterium avium subspecies paratuberculosis and beta Cell antigen zinc transporter 8 epitopes in sardinian type 1 diabetic patients with proliferative diabetic retinopathy
    Acta Ophthalmologica, 2013
    Co-Authors: Antonio Pinna, Speranza Masala, Francesco Blasetti, Irene Maiore, Davide Cossu, Daniela Paccagnini, E Brundu, La Sechi
    Abstract:

    Purpose Diabetic retinopathy (DR) is the leading cause of new cases of blindness in developed countries. ZnT8, a beta-Cell Membrane Protein involved in Zn++ transportation, may act as a major autoantigen in Type 1 Diabetes (T1D). Dysregulation in Zn++ homeostasis has been implicated in the pathogenesis of ischemia in DR. Mycobacterium avium subspecies paratuberculosis (MAP) causes an asymptomatic human infection transmitted from dairy herds through food contamination. MAP3865c, a MAP Cell Membrane Protein, has been shown to display a relevant sequence homology with ZnT8. Moreover, antibodies recognizing MAP3865c epitopes have been found to cross-react with ZnT8 in T1D patients. The purpose of this study was to detect serum antibodies against 6 highly immunogenic MAP3865c epitopes in T1D patients with proliferative diabetic retinopathy (PDR) and in healthy controls (HCs). Methods Blood samples were obtained from 23 T1D patients with PDR and 39 HCs. Antibodies against 2 trans-Membrane (MAP3865c125–133 MAP3865c133–141) and 4 C terminal (MAP3865c246–252, MAP3865c256–262, MAP3865c261–267 and MAP3865c281–287) peptides were detected by indirect ELISA. Fisher’s exact test and ROC curves were used to assess results. Results Antibodies against MAP3865c peptides were found in 6 out of 23 (26%) T1D patients with PDR and 2 out of 39 (5%) HCs, a statistically significant difference (p=0.04). Conclusion Results suggest that serum antibodies against MAP3865c peptides may play a role in the pathogenesis of PDR in T1D patients.Further larger studies are necessary to confirm these preliminary data.

Davide Cossu - One of the best experts on this subject based on the ideXlab platform.

  • detection of serum antibodies cross reacting with mycobacterium avium subspecies paratuberculosis and beta Cell antigen zinc transporter 8 homologous peptides in patients with high risk proliferative diabetic retinopathy
    PLOS ONE, 2014
    Co-Authors: Antonio Daniele Pinna, Speranza Masala, Francesco Blasetti, Irene Maiore, Davide Cossu, Daniela Paccagnini, Giuseppe Mameli, Leonardo Antonio Sechi
    Abstract:

    Purpose : MAP3865c, a Mycobacterium avium subspecies paratuberculosis (MAP) Cell Membrane Protein, has a relevant sequence homology with zinc transporter 8 (ZnT8), a beta-Cell Membrane Protein involved in Zn++ transportation. Recently, antibodies recognizing MAP3865c epitopes have been shown to cross-react with ZnT8 in type 1 diabetes patients. The purpose of this study was to detect antibodies against MAP3865c peptides in patients with high-risk proliferative diabetic retinopathy and speculate on whether they may somehow be involved in the pathogenesis of this severe retinal disorder. Methods : Blood samples were obtained from 62 type 1 and 80 type 2 diabetes patients with high-risk proliferative diabetic retinopathy and 81 healthy controls. Antibodies against 6 highly immunogenic MAP3865c peptides were detected by indirect ELISA. Results : Type 1 diabetes patients had significantly higher rates of positive antibodies than controls. Conversely, no statistically significant differences were found between type 2 diabetes patients and controls. After categorization of type 1 diabetes patients into two groups, one with positive, the other with negative antibodies, we found that they had similar mean visual acuity (∼0.6) and identical rates of vitreous hemorrhage (28.6%). Conversely, Hashimoto's thyroiditis prevalence was 4/13 (30.7%) in the positive antibody group and 1/49 (2%) in the negative antibody group, a statistically significant difference ( P = 0.016). Conclusions : This study confirmed that type 1 diabetes patients have significantly higher rates of positive antibodies against MAP/ZnT8 peptides, but failed to find a correlation between the presence of these antibodies and the severity degree of high-risk proliferative diabetic retinopathy. The significantly higher prevalence of Hashimoto's disease among type 1 diabetes patients with positive antibodies might suggest a possible common environmental trigger for these conditions.

  • detection of antibodies against homologous mycobacterium avium subspecies paratuberculosis and beta Cell antigen zinc transporter 8 epitopes in sardinian type 1 diabetic patients with proliferative diabetic retinopathy
    Acta Ophthalmologica, 2013
    Co-Authors: Antonio Pinna, Speranza Masala, Francesco Blasetti, Irene Maiore, Davide Cossu, Daniela Paccagnini, E Brundu, La Sechi
    Abstract:

    Purpose Diabetic retinopathy (DR) is the leading cause of new cases of blindness in developed countries. ZnT8, a beta-Cell Membrane Protein involved in Zn++ transportation, may act as a major autoantigen in Type 1 Diabetes (T1D). Dysregulation in Zn++ homeostasis has been implicated in the pathogenesis of ischemia in DR. Mycobacterium avium subspecies paratuberculosis (MAP) causes an asymptomatic human infection transmitted from dairy herds through food contamination. MAP3865c, a MAP Cell Membrane Protein, has been shown to display a relevant sequence homology with ZnT8. Moreover, antibodies recognizing MAP3865c epitopes have been found to cross-react with ZnT8 in T1D patients. The purpose of this study was to detect serum antibodies against 6 highly immunogenic MAP3865c epitopes in T1D patients with proliferative diabetic retinopathy (PDR) and in healthy controls (HCs). Methods Blood samples were obtained from 23 T1D patients with PDR and 39 HCs. Antibodies against 2 trans-Membrane (MAP3865c125–133 MAP3865c133–141) and 4 C terminal (MAP3865c246–252, MAP3865c256–262, MAP3865c261–267 and MAP3865c281–287) peptides were detected by indirect ELISA. Fisher’s exact test and ROC curves were used to assess results. Results Antibodies against MAP3865c peptides were found in 6 out of 23 (26%) T1D patients with PDR and 2 out of 39 (5%) HCs, a statistically significant difference (p=0.04). Conclusion Results suggest that serum antibodies against MAP3865c peptides may play a role in the pathogenesis of PDR in T1D patients.Further larger studies are necessary to confirm these preliminary data.