Healthy First-Degree Relatives of Patients with Type 1 Diabetes Exhibit Significant Differences in Basal Gene Expression Pattern of Immunocompetent Cells Compared to Controls: Expression Pattern as Predeterminant of Autoimmune Diabetes
Expression features of genetic landscape which predispose an individual to the type 1 diabetes are poorly understood. We addressed this question by comparing gene expression profile of freshly isolated peripheral blood mononuclear cells isolated from either patients with type 1 diabetes (T1D), or th...
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Veröffentlicht in: | Scandinavian journal of immunology 2012-02, Vol.75 (2), p.210-219 |
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creator | Stechova, K. Kolar, M. Blatny, R. Halbhuber, Z. Vcelakova, J. Hubackova, M. Petruzelkova, L. Sumnik, Z. Obermannova, B. Pithova, P. Stavikova, V. Krivjanska, M. Neuwirth, A. Kolouskova, S. Filipp, D. |
description | Expression features of genetic landscape which predispose an individual to the type 1 diabetes are poorly understood. We addressed this question by comparing gene expression profile of freshly isolated peripheral blood mononuclear cells isolated from either patients with type 1 diabetes (T1D), or their first‐degree relatives or healthy controls. Our aim was to establish whether a distinct type of ‘prodiabetogenic’ gene expression pattern in the group of relatives of patients with T1D could be identified. Whole‐genome expression profile of nine patients with T1D, their ten first‐degree relatives and ten healthy controls was analysed using the human high‐density expression microarray chip. Functional aspects of candidate genes were assessed using the MetaCore software. The highest number of differentially expressed genes (547) was found between the autoantibody‐negative healthy relatives and the healthy controls. Some of them represent genes critically involved in the regulation of innate immune responses such as TLR signalling and CCR3 signalling in eosinophiles, humoral immune reactions such as BCR pathway, costimulation and cytokine responses mediated by CD137, CD40 and CD28 signalling and IL‐1 proinflammatory pathway. Our data demonstrate that expression profile of healthy relatives of patients with T1D is clearly distinct from the pattern found in the healthy controls. That especially concerns differential activation status of genes and signalling pathways involved in proinflammatory processes and those of innate immunity and humoral reactivity. Thus, we posit that the study of the healthy relative’s gene expression pattern is instrumental for the identification of novel markers associated with the development of diabetes. |
doi_str_mv | 10.1111/j.1365-3083.2011.02637.x |
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We addressed this question by comparing gene expression profile of freshly isolated peripheral blood mononuclear cells isolated from either patients with type 1 diabetes (T1D), or their first‐degree relatives or healthy controls. Our aim was to establish whether a distinct type of ‘prodiabetogenic’ gene expression pattern in the group of relatives of patients with T1D could be identified. Whole‐genome expression profile of nine patients with T1D, their ten first‐degree relatives and ten healthy controls was analysed using the human high‐density expression microarray chip. Functional aspects of candidate genes were assessed using the MetaCore software. The highest number of differentially expressed genes (547) was found between the autoantibody‐negative healthy relatives and the healthy controls. Some of them represent genes critically involved in the regulation of innate immune responses such as TLR signalling and CCR3 signalling in eosinophiles, humoral immune reactions such as BCR pathway, costimulation and cytokine responses mediated by CD137, CD40 and CD28 signalling and IL‐1 proinflammatory pathway. Our data demonstrate that expression profile of healthy relatives of patients with T1D is clearly distinct from the pattern found in the healthy controls. That especially concerns differential activation status of genes and signalling pathways involved in proinflammatory processes and those of innate immunity and humoral reactivity. Thus, we posit that the study of the healthy relative’s gene expression pattern is instrumental for the identification of novel markers associated with the development of diabetes.</description><identifier>ISSN: 0300-9475</identifier><identifier>EISSN: 1365-3083</identifier><identifier>DOI: 10.1111/j.1365-3083.2011.02637.x</identifier><identifier>PMID: 21923738</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Adolescent ; Adult ; Antigens, CD - genetics ; Antigens, CD - immunology ; Autoantibodies - biosynthesis ; Autoantibodies - genetics ; Autoimmune diseases ; Autoimmunity ; Case-Control Studies ; CD137 antigen ; CD28 antigen ; CD40 antigen ; Child ; Child, Preschool ; Computer programs ; Data processing ; Diabetes mellitus ; Diabetes Mellitus, Type 1 - genetics ; Diabetes Mellitus, Type 1 - immunology ; Diabetes Mellitus, Type 1 - pathology ; Family ; Female ; Gene expression ; Gene Expression Profiling ; Gene Expression Regulation - immunology ; Genome-Wide Association Study ; Humans ; Immune response ; Immunity ; Immunity, Humoral ; Immunity, Innate ; Infant ; Inflammation ; Interleukin 1 ; Interleukin-1 - genetics ; Interleukin-1 - immunology ; Landscape ; Leukocytes, Mononuclear - immunology ; Leukocytes, Mononuclear - metabolism ; Leukocytes, Mononuclear - pathology ; Male ; Molecular Sequence Annotation ; Peripheral blood mononuclear cells ; Primary Cell Culture ; Receptors, CCR3 - genetics ; Receptors, CCR3 - immunology ; Signal Transduction ; software ; Toll-Like Receptors - genetics ; Toll-Like Receptors - immunology ; Transcription activation</subject><ispartof>Scandinavian journal of immunology, 2012-02, Vol.75 (2), p.210-219</ispartof><rights>2011 The Authors. Scandinavian Journal of Immunology © 2011 Blackwell Publishing Ltd</rights><rights>2011 The Authors. Scandinavian Journal of Immunology © 2011 Blackwell Publishing Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4897-f9873325285fe8f256bc6909630907bc15ef7e67dbecb3fb240a9e2577ce562a3</citedby><cites>FETCH-LOGICAL-c4897-f9873325285fe8f256bc6909630907bc15ef7e67dbecb3fb240a9e2577ce562a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1365-3083.2011.02637.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1365-3083.2011.02637.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,1433,27924,27925,45574,45575,46409,46833</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21923738$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Stechova, K.</creatorcontrib><creatorcontrib>Kolar, M.</creatorcontrib><creatorcontrib>Blatny, R.</creatorcontrib><creatorcontrib>Halbhuber, Z.</creatorcontrib><creatorcontrib>Vcelakova, J.</creatorcontrib><creatorcontrib>Hubackova, M.</creatorcontrib><creatorcontrib>Petruzelkova, L.</creatorcontrib><creatorcontrib>Sumnik, Z.</creatorcontrib><creatorcontrib>Obermannova, B.</creatorcontrib><creatorcontrib>Pithova, P.</creatorcontrib><creatorcontrib>Stavikova, V.</creatorcontrib><creatorcontrib>Krivjanska, M.</creatorcontrib><creatorcontrib>Neuwirth, A.</creatorcontrib><creatorcontrib>Kolouskova, S.</creatorcontrib><creatorcontrib>Filipp, D.</creatorcontrib><title>Healthy First-Degree Relatives of Patients with Type 1 Diabetes Exhibit Significant Differences in Basal Gene Expression Pattern of Immunocompetent Cells Compared to Controls: Expression Pattern as Predeterminant of Autoimmune Diabetes</title><title>Scandinavian journal of immunology</title><addtitle>Scand J Immunol</addtitle><description>Expression features of genetic landscape which predispose an individual to the type 1 diabetes are poorly understood. We addressed this question by comparing gene expression profile of freshly isolated peripheral blood mononuclear cells isolated from either patients with type 1 diabetes (T1D), or their first‐degree relatives or healthy controls. Our aim was to establish whether a distinct type of ‘prodiabetogenic’ gene expression pattern in the group of relatives of patients with T1D could be identified. Whole‐genome expression profile of nine patients with T1D, their ten first‐degree relatives and ten healthy controls was analysed using the human high‐density expression microarray chip. Functional aspects of candidate genes were assessed using the MetaCore software. The highest number of differentially expressed genes (547) was found between the autoantibody‐negative healthy relatives and the healthy controls. Some of them represent genes critically involved in the regulation of innate immune responses such as TLR signalling and CCR3 signalling in eosinophiles, humoral immune reactions such as BCR pathway, costimulation and cytokine responses mediated by CD137, CD40 and CD28 signalling and IL‐1 proinflammatory pathway. Our data demonstrate that expression profile of healthy relatives of patients with T1D is clearly distinct from the pattern found in the healthy controls. That especially concerns differential activation status of genes and signalling pathways involved in proinflammatory processes and those of innate immunity and humoral reactivity. Thus, we posit that the study of the healthy relative’s gene expression pattern is instrumental for the identification of novel markers associated with the development of diabetes.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Antigens, CD - genetics</subject><subject>Antigens, CD - immunology</subject><subject>Autoantibodies - biosynthesis</subject><subject>Autoantibodies - genetics</subject><subject>Autoimmune diseases</subject><subject>Autoimmunity</subject><subject>Case-Control Studies</subject><subject>CD137 antigen</subject><subject>CD28 antigen</subject><subject>CD40 antigen</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Computer programs</subject><subject>Data processing</subject><subject>Diabetes mellitus</subject><subject>Diabetes Mellitus, Type 1 - genetics</subject><subject>Diabetes Mellitus, Type 1 - immunology</subject><subject>Diabetes Mellitus, Type 1 - pathology</subject><subject>Family</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation - immunology</subject><subject>Genome-Wide Association Study</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immunity</subject><subject>Immunity, Humoral</subject><subject>Immunity, Innate</subject><subject>Infant</subject><subject>Inflammation</subject><subject>Interleukin 1</subject><subject>Interleukin-1 - genetics</subject><subject>Interleukin-1 - immunology</subject><subject>Landscape</subject><subject>Leukocytes, Mononuclear - immunology</subject><subject>Leukocytes, Mononuclear - metabolism</subject><subject>Leukocytes, Mononuclear - pathology</subject><subject>Male</subject><subject>Molecular Sequence Annotation</subject><subject>Peripheral blood mononuclear cells</subject><subject>Primary Cell Culture</subject><subject>Receptors, CCR3 - genetics</subject><subject>Receptors, CCR3 - immunology</subject><subject>Signal Transduction</subject><subject>software</subject><subject>Toll-Like Receptors - genetics</subject><subject>Toll-Like Receptors - immunology</subject><subject>Transcription activation</subject><issn>0300-9475</issn><issn>1365-3083</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNks9y0zAQxj0MDA2FV2B0g4td_YktixkOJWnSQAc6tFBuGtlZNQq2bCSlTZ6Zl0AmJSeGQRetZn_ft6vZTRJEcEbiOVlnhBV5ynDJMooJyTAtGM-2j5LRIfE4GWGGcSrGPD9Knnm_xpgwytnT5IgSQRln5Sj5eQ6qCasdmhnnQzqFWweAPkOjgrkDjzqNLmMINnh0b8IKXe96QARNjaogROBsuzKVCejK3FqjTa1siEmtwYGtY95Y9E551aA5WIh078B709nBNoCzQ4VF225sV3dtHy2jfgJN49EkvpWDJQpdjG1wXePf_M1BeXQZuah1rbFDA9HzdBM6M_jCodfnyROtGg8vHu7j5Mvs7Hpynl58mi8mpxdpPS4FT7UoOWM0p2WuodQ0L6q6EFgUDAvMq5rkoDkUfFlBXTFd0TFWAmjOeQ15QRU7Tl7tfXvX_diAD7I1vo5_Uha6jZeCYi7iMHAkX_-TJEXJeF6I8YCWe7R2nfcOtOydaZXbSYLlsBRyLYfZy2H2clgK-Xsp5DZKXz5U2VQtLA_CP1sQgbd74N40sPtvY3n1fjFEUZ_u9cYH2B70yn2XBY8fkDcf53L6jfMPN7OvMme_AAhE2YA</recordid><startdate>201202</startdate><enddate>201202</enddate><creator>Stechova, K.</creator><creator>Kolar, M.</creator><creator>Blatny, R.</creator><creator>Halbhuber, Z.</creator><creator>Vcelakova, J.</creator><creator>Hubackova, M.</creator><creator>Petruzelkova, L.</creator><creator>Sumnik, Z.</creator><creator>Obermannova, B.</creator><creator>Pithova, P.</creator><creator>Stavikova, V.</creator><creator>Krivjanska, M.</creator><creator>Neuwirth, A.</creator><creator>Kolouskova, S.</creator><creator>Filipp, D.</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</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>7X8</scope><scope>7T5</scope><scope>H94</scope></search><sort><creationdate>201202</creationdate><title>Healthy First-Degree Relatives of Patients with Type 1 Diabetes Exhibit Significant Differences in Basal Gene Expression Pattern of Immunocompetent Cells Compared to Controls: Expression Pattern as Predeterminant of Autoimmune Diabetes</title><author>Stechova, K. ; Kolar, M. ; Blatny, R. ; Halbhuber, Z. ; Vcelakova, J. ; Hubackova, M. ; Petruzelkova, L. ; Sumnik, Z. ; Obermannova, B. ; Pithova, P. ; Stavikova, V. ; Krivjanska, M. ; Neuwirth, A. ; Kolouskova, S. ; Filipp, D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4897-f9873325285fe8f256bc6909630907bc15ef7e67dbecb3fb240a9e2577ce562a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Antigens, CD - genetics</topic><topic>Antigens, CD - immunology</topic><topic>Autoantibodies - biosynthesis</topic><topic>Autoantibodies - genetics</topic><topic>Autoimmune diseases</topic><topic>Autoimmunity</topic><topic>Case-Control Studies</topic><topic>CD137 antigen</topic><topic>CD28 antigen</topic><topic>CD40 antigen</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Computer programs</topic><topic>Data processing</topic><topic>Diabetes mellitus</topic><topic>Diabetes Mellitus, Type 1 - genetics</topic><topic>Diabetes Mellitus, Type 1 - immunology</topic><topic>Diabetes Mellitus, Type 1 - pathology</topic><topic>Family</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation - immunology</topic><topic>Genome-Wide Association Study</topic><topic>Humans</topic><topic>Immune response</topic><topic>Immunity</topic><topic>Immunity, Humoral</topic><topic>Immunity, Innate</topic><topic>Infant</topic><topic>Inflammation</topic><topic>Interleukin 1</topic><topic>Interleukin-1 - genetics</topic><topic>Interleukin-1 - immunology</topic><topic>Landscape</topic><topic>Leukocytes, Mononuclear - immunology</topic><topic>Leukocytes, Mononuclear - metabolism</topic><topic>Leukocytes, Mononuclear - pathology</topic><topic>Male</topic><topic>Molecular Sequence Annotation</topic><topic>Peripheral blood mononuclear cells</topic><topic>Primary Cell Culture</topic><topic>Receptors, CCR3 - genetics</topic><topic>Receptors, CCR3 - immunology</topic><topic>Signal Transduction</topic><topic>software</topic><topic>Toll-Like Receptors - genetics</topic><topic>Toll-Like Receptors - immunology</topic><topic>Transcription activation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Stechova, K.</creatorcontrib><creatorcontrib>Kolar, M.</creatorcontrib><creatorcontrib>Blatny, R.</creatorcontrib><creatorcontrib>Halbhuber, Z.</creatorcontrib><creatorcontrib>Vcelakova, J.</creatorcontrib><creatorcontrib>Hubackova, M.</creatorcontrib><creatorcontrib>Petruzelkova, L.</creatorcontrib><creatorcontrib>Sumnik, Z.</creatorcontrib><creatorcontrib>Obermannova, B.</creatorcontrib><creatorcontrib>Pithova, P.</creatorcontrib><creatorcontrib>Stavikova, V.</creatorcontrib><creatorcontrib>Krivjanska, M.</creatorcontrib><creatorcontrib>Neuwirth, A.</creatorcontrib><creatorcontrib>Kolouskova, S.</creatorcontrib><creatorcontrib>Filipp, D.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Scandinavian journal of immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Stechova, K.</au><au>Kolar, M.</au><au>Blatny, R.</au><au>Halbhuber, Z.</au><au>Vcelakova, J.</au><au>Hubackova, M.</au><au>Petruzelkova, L.</au><au>Sumnik, Z.</au><au>Obermannova, B.</au><au>Pithova, P.</au><au>Stavikova, V.</au><au>Krivjanska, M.</au><au>Neuwirth, A.</au><au>Kolouskova, S.</au><au>Filipp, D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Healthy First-Degree Relatives of Patients with Type 1 Diabetes Exhibit Significant Differences in Basal Gene Expression Pattern of Immunocompetent Cells Compared to Controls: Expression Pattern as Predeterminant of Autoimmune Diabetes</atitle><jtitle>Scandinavian journal of immunology</jtitle><addtitle>Scand J Immunol</addtitle><date>2012-02</date><risdate>2012</risdate><volume>75</volume><issue>2</issue><spage>210</spage><epage>219</epage><pages>210-219</pages><issn>0300-9475</issn><eissn>1365-3083</eissn><abstract>Expression features of genetic landscape which predispose an individual to the type 1 diabetes are poorly understood. We addressed this question by comparing gene expression profile of freshly isolated peripheral blood mononuclear cells isolated from either patients with type 1 diabetes (T1D), or their first‐degree relatives or healthy controls. Our aim was to establish whether a distinct type of ‘prodiabetogenic’ gene expression pattern in the group of relatives of patients with T1D could be identified. Whole‐genome expression profile of nine patients with T1D, their ten first‐degree relatives and ten healthy controls was analysed using the human high‐density expression microarray chip. Functional aspects of candidate genes were assessed using the MetaCore software. The highest number of differentially expressed genes (547) was found between the autoantibody‐negative healthy relatives and the healthy controls. Some of them represent genes critically involved in the regulation of innate immune responses such as TLR signalling and CCR3 signalling in eosinophiles, humoral immune reactions such as BCR pathway, costimulation and cytokine responses mediated by CD137, CD40 and CD28 signalling and IL‐1 proinflammatory pathway. Our data demonstrate that expression profile of healthy relatives of patients with T1D is clearly distinct from the pattern found in the healthy controls. That especially concerns differential activation status of genes and signalling pathways involved in proinflammatory processes and those of innate immunity and humoral reactivity. Thus, we posit that the study of the healthy relative’s gene expression pattern is instrumental for the identification of novel markers associated with the development of diabetes.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>21923738</pmid><doi>10.1111/j.1365-3083.2011.02637.x</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adolescent Adult Antigens, CD - genetics Antigens, CD - immunology Autoantibodies - biosynthesis Autoantibodies - genetics Autoimmune diseases Autoimmunity Case-Control Studies CD137 antigen CD28 antigen CD40 antigen Child Child, Preschool Computer programs Data processing Diabetes mellitus Diabetes Mellitus, Type 1 - genetics Diabetes Mellitus, Type 1 - immunology Diabetes Mellitus, Type 1 - pathology Family Female Gene expression Gene Expression Profiling Gene Expression Regulation - immunology Genome-Wide Association Study Humans Immune response Immunity Immunity, Humoral Immunity, Innate Infant Inflammation Interleukin 1 Interleukin-1 - genetics Interleukin-1 - immunology Landscape Leukocytes, Mononuclear - immunology Leukocytes, Mononuclear - metabolism Leukocytes, Mononuclear - pathology Male Molecular Sequence Annotation Peripheral blood mononuclear cells Primary Cell Culture Receptors, CCR3 - genetics Receptors, CCR3 - immunology Signal Transduction software Toll-Like Receptors - genetics Toll-Like Receptors - immunology Transcription activation |
title | Healthy First-Degree Relatives of Patients with Type 1 Diabetes Exhibit Significant Differences in Basal Gene Expression Pattern of Immunocompetent Cells Compared to Controls: Expression Pattern as Predeterminant of Autoimmune Diabetes |
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