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Anti-GAD65 reactive peripheral blood mononuclear cells in the pathogenesis of cystic fibrosis related diabetes mellitus
Objective: A role of autoreactive T cells for type 1 diabetes pathogenesis is considered crucial. In our pilot study we addressed if autoreactive mononuclear cells are present also in peripheral blood of patients with other specific forms of diabetes as cystic fibrosis related diabetes (CFRD). Metho...
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| Published in: | Autoimmunity (Chur, Switzerland) Switzerland), 2005-06, Vol.38 (4), p.319-323 |
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| creator | Stechova, Katerina Kolouskova, Stanislava Sumnik, Zdenek Cinek, Ondrej Kverka, Miloslav Karlsson Faresj, Maria Chudoba, Daniel Dovolilova, Eva Pechova, Marta Vrabelova, Zuzana Böhmova, Kristyna Janecek, Lukas Saudek, Frantisek Vavrinec, Jan |
| description | Objective: A role of autoreactive T cells for type 1 diabetes pathogenesis is considered crucial. In our pilot study we addressed if autoreactive mononuclear cells are present also in peripheral blood of patients with other specific forms of diabetes as cystic fibrosis related diabetes (CFRD). Methods: Cellular immune responses to a known β-cell autoantigen (GAD65 and GAD65 derived peptides) were analysed by ELISPOT (IFN-γ) and by protein microarray analysis in four patients suffering from CFRD, in four cystic fibrosis (CF) patients without diabetes, in eight type 1 diabetes patients (without CF) and in four healthy controls. Results: Response to the autoantigen GAD65 (protein and peptides) was observed in 7/8 patients suffering from CF and in all type 1 diabetes patients. Post-stimulation production of Th1 cytokines (IFN-γ, TNF-β) was observed in 2/4 CFRD, 1/4 CF patients and in 7/8 type 1 diabetes patients. All these patients carry prodiabetogenic HLA-DQ genotype. Th2- and Th3 type of cytokine pattern was observed in 2/4 CF patients. Production of IL-8 was observed in the third CFRD as well as in the third CF patient and in 1/8 type 1 diabetes patient and borderline production of this chemokine was also observed in 2/4 healthy controls. No reaction was observed in the other 2/4 healthy controls and in the fourth CFRD patient who carried a strongly protective genotype and did not produce autoantibodies. The most potent peptide of GAD65 was amino acids 509-528. Conclusions: We consider our observations as a sign of a reaction directed against the self-antigen GAD65 that are closely connected to type 1 diabetes. In CF patients who do not develop diabetes autoreactive mechanisms are very probably efficiently suppressed by immune self-tolerance mechanisms. CFRD patients are a heterogenic group. To disclose those who may display features of autoimmune diabetes could have an impact for their therapy and prognosis. |
| doi_str_mv | 10.1080/08916930500124387 |
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In our pilot study we addressed if autoreactive mononuclear cells are present also in peripheral blood of patients with other specific forms of diabetes as cystic fibrosis related diabetes (CFRD). Methods: Cellular immune responses to a known β-cell autoantigen (GAD65 and GAD65 derived peptides) were analysed by ELISPOT (IFN-γ) and by protein microarray analysis in four patients suffering from CFRD, in four cystic fibrosis (CF) patients without diabetes, in eight type 1 diabetes patients (without CF) and in four healthy controls. Results: Response to the autoantigen GAD65 (protein and peptides) was observed in 7/8 patients suffering from CF and in all type 1 diabetes patients. Post-stimulation production of Th1 cytokines (IFN-γ, TNF-β) was observed in 2/4 CFRD, 1/4 CF patients and in 7/8 type 1 diabetes patients. All these patients carry prodiabetogenic HLA-DQ genotype. Th2- and Th3 type of cytokine pattern was observed in 2/4 CF patients. Production of IL-8 was observed in the third CFRD as well as in the third CF patient and in 1/8 type 1 diabetes patient and borderline production of this chemokine was also observed in 2/4 healthy controls. No reaction was observed in the other 2/4 healthy controls and in the fourth CFRD patient who carried a strongly protective genotype and did not produce autoantibodies. The most potent peptide of GAD65 was amino acids 509-528. Conclusions: We consider our observations as a sign of a reaction directed against the self-antigen GAD65 that are closely connected to type 1 diabetes. In CF patients who do not develop diabetes autoreactive mechanisms are very probably efficiently suppressed by immune self-tolerance mechanisms. CFRD patients are a heterogenic group. To disclose those who may display features of autoimmune diabetes could have an impact for their therapy and prognosis.</description><identifier>ISSN: 0891-6934</identifier><identifier>ISSN: 1607-842X</identifier><identifier>EISSN: 1607-842X</identifier><identifier>DOI: 10.1080/08916930500124387</identifier><identifier>PMID: 16206514</identifier><language>eng</language><publisher>Abingdon: Informa UK Ltd</publisher><subject>Adolescent ; Adult ; Autoantibodies - blood ; Autoantibodies - immunology ; autoimmunity ; Biological and medical sciences ; cellular response ; Child ; cystic fibrosis ; Cystic Fibrosis - complications ; Cystic Fibrosis - immunology ; cytokines ; Diabetes ; Diabetes Mellitus - etiology ; Diabetes Mellitus - immunology ; Female ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; General aspects ; Glutamate Decarboxylase - immunology ; HLA-DQ Antigens - immunology ; Humans ; Immunopathology ; Interferon-gamma - blood ; Interleukin-8 - blood ; Isoenzymes - immunology ; Leukocytes, Mononuclear - immunology ; Lymphotoxin-alpha - blood ; Male ; Medical sciences ; MEDICIN ; MEDICINE ; Pilot Projects ; Protein Array Analysis</subject><ispartof>Autoimmunity (Chur, Switzerland), 2005-06, Vol.38 (4), p.319-323</ispartof><rights>2005 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted 2005</rights><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c502t-c74828e28ac6b30ae71cf0d5ec5a7f154f6f24dc72857d8b9ff9b7e2370e0de23</citedby><cites>FETCH-LOGICAL-c502t-c74828e28ac6b30ae71cf0d5ec5a7f154f6f24dc72857d8b9ff9b7e2370e0de23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,786,790,891,27957,27958</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16902900$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16206514$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-28873$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Stechova, Katerina</creatorcontrib><creatorcontrib>Kolouskova, Stanislava</creatorcontrib><creatorcontrib>Sumnik, Zdenek</creatorcontrib><creatorcontrib>Cinek, Ondrej</creatorcontrib><creatorcontrib>Kverka, Miloslav</creatorcontrib><creatorcontrib>Karlsson Faresj, Maria</creatorcontrib><creatorcontrib>Chudoba, Daniel</creatorcontrib><creatorcontrib>Dovolilova, Eva</creatorcontrib><creatorcontrib>Pechova, Marta</creatorcontrib><creatorcontrib>Vrabelova, Zuzana</creatorcontrib><creatorcontrib>Böhmova, Kristyna</creatorcontrib><creatorcontrib>Janecek, Lukas</creatorcontrib><creatorcontrib>Saudek, Frantisek</creatorcontrib><creatorcontrib>Vavrinec, Jan</creatorcontrib><title>Anti-GAD65 reactive peripheral blood mononuclear cells in the pathogenesis of cystic fibrosis related diabetes mellitus</title><title>Autoimmunity (Chur, Switzerland)</title><addtitle>Autoimmunity</addtitle><description>Objective: A role of autoreactive T cells for type 1 diabetes pathogenesis is considered crucial. In our pilot study we addressed if autoreactive mononuclear cells are present also in peripheral blood of patients with other specific forms of diabetes as cystic fibrosis related diabetes (CFRD). Methods: Cellular immune responses to a known β-cell autoantigen (GAD65 and GAD65 derived peptides) were analysed by ELISPOT (IFN-γ) and by protein microarray analysis in four patients suffering from CFRD, in four cystic fibrosis (CF) patients without diabetes, in eight type 1 diabetes patients (without CF) and in four healthy controls. Results: Response to the autoantigen GAD65 (protein and peptides) was observed in 7/8 patients suffering from CF and in all type 1 diabetes patients. Post-stimulation production of Th1 cytokines (IFN-γ, TNF-β) was observed in 2/4 CFRD, 1/4 CF patients and in 7/8 type 1 diabetes patients. All these patients carry prodiabetogenic HLA-DQ genotype. Th2- and Th3 type of cytokine pattern was observed in 2/4 CF patients. Production of IL-8 was observed in the third CFRD as well as in the third CF patient and in 1/8 type 1 diabetes patient and borderline production of this chemokine was also observed in 2/4 healthy controls. No reaction was observed in the other 2/4 healthy controls and in the fourth CFRD patient who carried a strongly protective genotype and did not produce autoantibodies. The most potent peptide of GAD65 was amino acids 509-528. Conclusions: We consider our observations as a sign of a reaction directed against the self-antigen GAD65 that are closely connected to type 1 diabetes. In CF patients who do not develop diabetes autoreactive mechanisms are very probably efficiently suppressed by immune self-tolerance mechanisms. CFRD patients are a heterogenic group. To disclose those who may display features of autoimmune diabetes could have an impact for their therapy and prognosis.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Autoantibodies - blood</subject><subject>Autoantibodies - immunology</subject><subject>autoimmunity</subject><subject>Biological and medical sciences</subject><subject>cellular response</subject><subject>Child</subject><subject>cystic fibrosis</subject><subject>Cystic Fibrosis - complications</subject><subject>Cystic Fibrosis - immunology</subject><subject>cytokines</subject><subject>Diabetes</subject><subject>Diabetes Mellitus - etiology</subject><subject>Diabetes Mellitus - immunology</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>General aspects</subject><subject>Glutamate Decarboxylase - immunology</subject><subject>HLA-DQ Antigens - immunology</subject><subject>Humans</subject><subject>Immunopathology</subject><subject>Interferon-gamma - blood</subject><subject>Interleukin-8 - blood</subject><subject>Isoenzymes - immunology</subject><subject>Leukocytes, Mononuclear - immunology</subject><subject>Lymphotoxin-alpha - blood</subject><subject>Male</subject><subject>Medical sciences</subject><subject>MEDICIN</subject><subject>MEDICINE</subject><subject>Pilot Projects</subject><subject>Protein Array Analysis</subject><issn>0891-6934</issn><issn>1607-842X</issn><issn>1607-842X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><recordid>eNqFkU1v1DAQhiMEoqXwA7ggX-BEYOwktiN6WbVQkCpxAcTNcpxx15UTL7bDav89Xu3yJaRyGsl-ntHMvFX1lMIrChJeg-wp7xvoAChrGynuVaeUg6hly77er073_3UB2pPqUUq3AMAEbx9WJ5Qz4B1tT6vtas6uvlpd8o5E1Ca770g2GN1mjVF7MvgQRjKFOcyL8agjMeh9Im4meV1IndfhBmdMLpFgidml7Ayxbohh_xTR64wjGZ0eMGMiU7FdXtLj6oHVPuGTYz2rPr97--nifX398erDxeq6Nh2wXBvRSiaRSW340IBGQY2FsUPTaWFp11puWTsawWQnRjn01vaDQNYIQBhLPateHvqmLW6WQW2im3TcqaCdunRfVirEG-XdopiUoin4iwO-ieHbgimryaX9xnrGsCTFJe8El_8HqWCt7KEvID2AplwkRbS_RqCg9imqf1IszrNj82WYcPxtHGMrwPMjoJPR3kY9G5f-4HpgPUDhzg-cm22Ik96G6EeV9c6H-FNq7prjzV_6GrXPa6MjqtuwxLkEd8cWPwB9-MvI</recordid><startdate>20050601</startdate><enddate>20050601</enddate><creator>Stechova, Katerina</creator><creator>Kolouskova, Stanislava</creator><creator>Sumnik, Zdenek</creator><creator>Cinek, Ondrej</creator><creator>Kverka, Miloslav</creator><creator>Karlsson Faresj, Maria</creator><creator>Chudoba, Daniel</creator><creator>Dovolilova, Eva</creator><creator>Pechova, Marta</creator><creator>Vrabelova, Zuzana</creator><creator>Böhmova, Kristyna</creator><creator>Janecek, Lukas</creator><creator>Saudek, Frantisek</creator><creator>Vavrinec, Jan</creator><general>Informa UK Ltd</general><general>Taylor & Francis</general><general>Taylor and Francis</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>DG8</scope></search><sort><creationdate>20050601</creationdate><title>Anti-GAD65 reactive peripheral blood mononuclear cells in the pathogenesis of cystic fibrosis related diabetes mellitus</title><author>Stechova, Katerina ; Kolouskova, Stanislava ; Sumnik, Zdenek ; Cinek, Ondrej ; Kverka, Miloslav ; Karlsson Faresj, Maria ; Chudoba, Daniel ; Dovolilova, Eva ; Pechova, Marta ; Vrabelova, Zuzana ; Böhmova, Kristyna ; Janecek, Lukas ; Saudek, Frantisek ; Vavrinec, Jan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c502t-c74828e28ac6b30ae71cf0d5ec5a7f154f6f24dc72857d8b9ff9b7e2370e0de23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Autoantibodies - blood</topic><topic>Autoantibodies - immunology</topic><topic>autoimmunity</topic><topic>Biological and medical sciences</topic><topic>cellular response</topic><topic>Child</topic><topic>cystic fibrosis</topic><topic>Cystic Fibrosis - complications</topic><topic>Cystic Fibrosis - immunology</topic><topic>cytokines</topic><topic>Diabetes</topic><topic>Diabetes Mellitus - etiology</topic><topic>Diabetes Mellitus - immunology</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>General aspects</topic><topic>Glutamate Decarboxylase - immunology</topic><topic>HLA-DQ Antigens - immunology</topic><topic>Humans</topic><topic>Immunopathology</topic><topic>Interferon-gamma - blood</topic><topic>Interleukin-8 - blood</topic><topic>Isoenzymes - immunology</topic><topic>Leukocytes, Mononuclear - immunology</topic><topic>Lymphotoxin-alpha - blood</topic><topic>Male</topic><topic>Medical sciences</topic><topic>MEDICIN</topic><topic>MEDICINE</topic><topic>Pilot Projects</topic><topic>Protein Array Analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Stechova, Katerina</creatorcontrib><creatorcontrib>Kolouskova, Stanislava</creatorcontrib><creatorcontrib>Sumnik, Zdenek</creatorcontrib><creatorcontrib>Cinek, Ondrej</creatorcontrib><creatorcontrib>Kverka, Miloslav</creatorcontrib><creatorcontrib>Karlsson Faresj, Maria</creatorcontrib><creatorcontrib>Chudoba, Daniel</creatorcontrib><creatorcontrib>Dovolilova, Eva</creatorcontrib><creatorcontrib>Pechova, Marta</creatorcontrib><creatorcontrib>Vrabelova, Zuzana</creatorcontrib><creatorcontrib>Böhmova, Kristyna</creatorcontrib><creatorcontrib>Janecek, Lukas</creatorcontrib><creatorcontrib>Saudek, Frantisek</creatorcontrib><creatorcontrib>Vavrinec, Jan</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Linköpings universitet</collection><jtitle>Autoimmunity (Chur, Switzerland)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Stechova, Katerina</au><au>Kolouskova, Stanislava</au><au>Sumnik, Zdenek</au><au>Cinek, Ondrej</au><au>Kverka, Miloslav</au><au>Karlsson Faresj, Maria</au><au>Chudoba, Daniel</au><au>Dovolilova, Eva</au><au>Pechova, Marta</au><au>Vrabelova, Zuzana</au><au>Böhmova, Kristyna</au><au>Janecek, Lukas</au><au>Saudek, Frantisek</au><au>Vavrinec, Jan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Anti-GAD65 reactive peripheral blood mononuclear cells in the pathogenesis of cystic fibrosis related diabetes mellitus</atitle><jtitle>Autoimmunity (Chur, Switzerland)</jtitle><addtitle>Autoimmunity</addtitle><date>2005-06-01</date><risdate>2005</risdate><volume>38</volume><issue>4</issue><spage>319</spage><epage>323</epage><pages>319-323</pages><issn>0891-6934</issn><issn>1607-842X</issn><eissn>1607-842X</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Objective: A role of autoreactive T cells for type 1 diabetes pathogenesis is considered crucial. In our pilot study we addressed if autoreactive mononuclear cells are present also in peripheral blood of patients with other specific forms of diabetes as cystic fibrosis related diabetes (CFRD). Methods: Cellular immune responses to a known β-cell autoantigen (GAD65 and GAD65 derived peptides) were analysed by ELISPOT (IFN-γ) and by protein microarray analysis in four patients suffering from CFRD, in four cystic fibrosis (CF) patients without diabetes, in eight type 1 diabetes patients (without CF) and in four healthy controls. Results: Response to the autoantigen GAD65 (protein and peptides) was observed in 7/8 patients suffering from CF and in all type 1 diabetes patients. Post-stimulation production of Th1 cytokines (IFN-γ, TNF-β) was observed in 2/4 CFRD, 1/4 CF patients and in 7/8 type 1 diabetes patients. All these patients carry prodiabetogenic HLA-DQ genotype. Th2- and Th3 type of cytokine pattern was observed in 2/4 CF patients. Production of IL-8 was observed in the third CFRD as well as in the third CF patient and in 1/8 type 1 diabetes patient and borderline production of this chemokine was also observed in 2/4 healthy controls. No reaction was observed in the other 2/4 healthy controls and in the fourth CFRD patient who carried a strongly protective genotype and did not produce autoantibodies. The most potent peptide of GAD65 was amino acids 509-528. Conclusions: We consider our observations as a sign of a reaction directed against the self-antigen GAD65 that are closely connected to type 1 diabetes. In CF patients who do not develop diabetes autoreactive mechanisms are very probably efficiently suppressed by immune self-tolerance mechanisms. CFRD patients are a heterogenic group. To disclose those who may display features of autoimmune diabetes could have an impact for their therapy and prognosis.</abstract><cop>Abingdon</cop><pub>Informa UK Ltd</pub><pmid>16206514</pmid><doi>10.1080/08916930500124387</doi><tpages>5</tpages></addata></record> |
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| ispartof | Autoimmunity (Chur, Switzerland), 2005-06, Vol.38 (4), p.319-323 |
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| source | Taylor and Francis:Jisc Collections:Taylor and Francis Read and Publish Agreement 2024-2025:Medical Collection (Reading list) |
| subjects | Adolescent Adult Autoantibodies - blood Autoantibodies - immunology autoimmunity Biological and medical sciences cellular response Child cystic fibrosis Cystic Fibrosis - complications Cystic Fibrosis - immunology cytokines Diabetes Diabetes Mellitus - etiology Diabetes Mellitus - immunology Female Fundamental and applied biological sciences. Psychology Fundamental immunology General aspects Glutamate Decarboxylase - immunology HLA-DQ Antigens - immunology Humans Immunopathology Interferon-gamma - blood Interleukin-8 - blood Isoenzymes - immunology Leukocytes, Mononuclear - immunology Lymphotoxin-alpha - blood Male Medical sciences MEDICIN MEDICINE Pilot Projects Protein Array Analysis |
| title | Anti-GAD65 reactive peripheral blood mononuclear cells in the pathogenesis of cystic fibrosis related diabetes mellitus |
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