Distinct profiles of Sjögren's syndrome patients with ectopic salivary gland germinal centers revealed by serum cytokines and BAFF
The formation of ectopic germinal centers (GC) has been described in Sjögren's syndrome (SS), although little is known about the molecular basis of this phenomenon. These structures are a focus of in situ autoantibody production and have been hypothesized to be involved in lymphomagenesis in SS...
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Veröffentlicht in: | Clinical Immunology 2005-11, Vol.117 (2), p.168-176 |
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description | The formation of ectopic germinal centers (GC) has been described in Sjögren's syndrome (SS), although little is known about the molecular basis of this phenomenon. These structures are a focus of in situ autoantibody production and have been hypothesized to be involved in lymphomagenesis in SS patients. Serum cytokines also play an important role in SS pathogenesis in part via immune dysregulation and may therefore contribute to ectopic GC formation. Herein, highly multiplex cytokine screening of SS patients with (SSGC+) and without (SSGC−) GC formation was done to identify cytokine profiles that correlate with this phenomenon. Serum levels of B-cell activating factor (BAFF) were also screened as a potential biomarker of immune dysregulation in SS and SSGC formation. Univariate analysis demonstrated that serum levels of a broad spectrum of immune and inflammatory modulating cytokines are upregulated in SSGC+ and SSGC− patients relative to unaffected controls IL-1β, IL−2, IL-6, IL-15, IFN-γ and CCL4 (MIP-1β). SSGC+ patients were distinguished from healthy individuals by higher levels of IL-4, IL-10, GM-CSF, IFN-α, CCL3 (MIP-1α), CCL11 (Eotaxin) and BAFF, while SSGC+ and SSGC− patients differed in CCL2 (MCP-1) expression. Discriminant function analysis (DFA), a multivariate discrimination method that uses observed differences to characterize groups when casual relationships are not well understood, was employed to identify a subset of these biomarkers that maximally discriminate among SSGC+, SSGC− and unaffected individuals. The biomarker having the strongest discriminatory power identified by DFA besides CCL11 (Eotaxin) and IFN-γ was BAFF. The variables identified by DFA are interdependent and are often of mechanistic significance to the pathologic states they distinguish, suggesting that these factors modulate SS pathology and SSGC formation in a synergistic manner. |
doi_str_mv | 10.1016/j.clim.2005.06.016 |
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These structures are a focus of in situ autoantibody production and have been hypothesized to be involved in lymphomagenesis in SS patients. Serum cytokines also play an important role in SS pathogenesis in part via immune dysregulation and may therefore contribute to ectopic GC formation. Herein, highly multiplex cytokine screening of SS patients with (SSGC+) and without (SSGC−) GC formation was done to identify cytokine profiles that correlate with this phenomenon. Serum levels of B-cell activating factor (BAFF) were also screened as a potential biomarker of immune dysregulation in SS and SSGC formation. Univariate analysis demonstrated that serum levels of a broad spectrum of immune and inflammatory modulating cytokines are upregulated in SSGC+ and SSGC− patients relative to unaffected controls IL-1β, IL−2, IL-6, IL-15, IFN-γ and CCL4 (MIP-1β). SSGC+ patients were distinguished from healthy individuals by higher levels of IL-4, IL-10, GM-CSF, IFN-α, CCL3 (MIP-1α), CCL11 (Eotaxin) and BAFF, while SSGC+ and SSGC− patients differed in CCL2 (MCP-1) expression. Discriminant function analysis (DFA), a multivariate discrimination method that uses observed differences to characterize groups when casual relationships are not well understood, was employed to identify a subset of these biomarkers that maximally discriminate among SSGC+, SSGC− and unaffected individuals. The biomarker having the strongest discriminatory power identified by DFA besides CCL11 (Eotaxin) and IFN-γ was BAFF. The variables identified by DFA are interdependent and are often of mechanistic significance to the pathologic states they distinguish, suggesting that these factors modulate SS pathology and SSGC formation in a synergistic manner.</description><identifier>ISSN: 1521-6616</identifier><identifier>EISSN: 1521-7035</identifier><identifier>EISSN: 1365-2567</identifier><identifier>DOI: 10.1016/j.clim.2005.06.016</identifier><identifier>PMID: 16126006</identifier><identifier>CODEN: CLIIFY</identifier><language>eng</language><publisher>San Diego, CA: Elsevier Inc</publisher><subject>Adult ; B-Cell Activating Factor ; Biological and medical sciences ; Choristoma - immunology ; Circulating cytokines ; Cluster Analysis ; Cytokines - biosynthesis ; Cytokines - blood ; Ectopic germinal center ; Female ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Germinal Center - immunology ; Germinal Center - pathology ; Humans ; Immunopathology ; Medical sciences ; Membrane Proteins - biosynthesis ; Membrane Proteins - blood ; Middle Aged ; Multivariate Analysis ; Salivary Gland Diseases - immunology ; Salivary Glands, Minor - immunology ; Sjogren's Syndrome - blood ; Sjogren's Syndrome - immunology ; Sjogren's Syndrome - pathology ; Sjögren's syndrome ; Tumor Necrosis Factor-alpha - biosynthesis</subject><ispartof>Clinical Immunology, 2005-11, Vol.117 (2), p.168-176</ispartof><rights>2005 Elsevier Inc.</rights><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c415t-8bcf33402396874a847c7efb0e64b37445b4635379d8dcd405716bce77a400ec3</citedby><cites>FETCH-LOGICAL-c415t-8bcf33402396874a847c7efb0e64b37445b4635379d8dcd405716bce77a400ec3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.clim.2005.06.016$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17206036$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16126006$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Szodoray, Peter</creatorcontrib><creatorcontrib>Alex, Philip</creatorcontrib><creatorcontrib>Jonsson, Malin V.</creatorcontrib><creatorcontrib>Knowlton, Nicholas</creatorcontrib><creatorcontrib>Dozmorov, Igor</creatorcontrib><creatorcontrib>Nakken, Britt</creatorcontrib><creatorcontrib>Delaleu, Nicolas</creatorcontrib><creatorcontrib>Jonsson, Roland</creatorcontrib><creatorcontrib>Centola, Michael</creatorcontrib><title>Distinct profiles of Sjögren's syndrome patients with ectopic salivary gland germinal centers revealed by serum cytokines and BAFF</title><title>Clinical Immunology</title><addtitle>Clin Immunol</addtitle><description>The formation of ectopic germinal centers (GC) has been described in Sjögren's syndrome (SS), although little is known about the molecular basis of this phenomenon. These structures are a focus of in situ autoantibody production and have been hypothesized to be involved in lymphomagenesis in SS patients. Serum cytokines also play an important role in SS pathogenesis in part via immune dysregulation and may therefore contribute to ectopic GC formation. Herein, highly multiplex cytokine screening of SS patients with (SSGC+) and without (SSGC−) GC formation was done to identify cytokine profiles that correlate with this phenomenon. Serum levels of B-cell activating factor (BAFF) were also screened as a potential biomarker of immune dysregulation in SS and SSGC formation. Univariate analysis demonstrated that serum levels of a broad spectrum of immune and inflammatory modulating cytokines are upregulated in SSGC+ and SSGC− patients relative to unaffected controls IL-1β, IL−2, IL-6, IL-15, IFN-γ and CCL4 (MIP-1β). SSGC+ patients were distinguished from healthy individuals by higher levels of IL-4, IL-10, GM-CSF, IFN-α, CCL3 (MIP-1α), CCL11 (Eotaxin) and BAFF, while SSGC+ and SSGC− patients differed in CCL2 (MCP-1) expression. Discriminant function analysis (DFA), a multivariate discrimination method that uses observed differences to characterize groups when casual relationships are not well understood, was employed to identify a subset of these biomarkers that maximally discriminate among SSGC+, SSGC− and unaffected individuals. The biomarker having the strongest discriminatory power identified by DFA besides CCL11 (Eotaxin) and IFN-γ was BAFF. 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Psychology</subject><subject>Fundamental immunology</subject><subject>Germinal Center - immunology</subject><subject>Germinal Center - pathology</subject><subject>Humans</subject><subject>Immunopathology</subject><subject>Medical sciences</subject><subject>Membrane Proteins - biosynthesis</subject><subject>Membrane Proteins - blood</subject><subject>Middle Aged</subject><subject>Multivariate Analysis</subject><subject>Salivary Gland Diseases - immunology</subject><subject>Salivary Glands, Minor - immunology</subject><subject>Sjogren's Syndrome - blood</subject><subject>Sjogren's Syndrome - immunology</subject><subject>Sjogren's Syndrome - pathology</subject><subject>Sjögren's syndrome</subject><subject>Tumor Necrosis Factor-alpha - biosynthesis</subject><issn>1521-6616</issn><issn>1521-7035</issn><issn>1365-2567</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc-O0zAQhy0EYpeFF-CAfAFODePYsVOJy7JQQFqJA3C2HHtSXPKneNKinnknXoAXw1Ej7Q1Otkbfbzyej7GnAgoBQr_aFb6LfVECVAXoIpfusUtRlWJlQFb3l7vWQl-wR0Q7yGBZ6ofsQmhRagB9yX69jTTFwU98n8Y2dkh8bPnn3Z_f24TDS-J0GkIae-R7N0UcJuI_4_SNo5_GffScXBePLp34tnND4FtMfRxcx31GMRFPeETXYeDNiROmQ8_9aRq_xyE_NAfeXG82j9mD1nWET5bzin3dvPty82F1--n9x5vr25VXoppWdeNbKRWUcq1ro1ytjDfYNoBaNdIoVTVKy0qadaiDDwoqI3Tj0RinANDLK_bi3Dd_9ccBabJ9JI9dnhzHA1ldayPkGv4LirWSlahmsDyDPo1ECVu7T7HP67AC7OzI7uzsyM6OLGibSzn0bOl-aHoMd5FFSgaeL4Aj77o2ucFHuuNMCRrkzL0-c5iXdoyYLPmsyGOIKfuxYYz_muMvgNqxdA</recordid><startdate>20051101</startdate><enddate>20051101</enddate><creator>Szodoray, Peter</creator><creator>Alex, Philip</creator><creator>Jonsson, Malin V.</creator><creator>Knowlton, Nicholas</creator><creator>Dozmorov, Igor</creator><creator>Nakken, Britt</creator><creator>Delaleu, Nicolas</creator><creator>Jonsson, Roland</creator><creator>Centola, Michael</creator><general>Elsevier Inc</general><general>Elsevier</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></search><sort><creationdate>20051101</creationdate><title>Distinct profiles of Sjögren's syndrome patients with ectopic salivary gland germinal centers revealed by serum cytokines and BAFF</title><author>Szodoray, Peter ; Alex, Philip ; Jonsson, Malin V. ; Knowlton, Nicholas ; Dozmorov, Igor ; Nakken, Britt ; Delaleu, Nicolas ; Jonsson, Roland ; Centola, Michael</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c415t-8bcf33402396874a847c7efb0e64b37445b4635379d8dcd405716bce77a400ec3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Adult</topic><topic>B-Cell Activating Factor</topic><topic>Biological and medical sciences</topic><topic>Choristoma - immunology</topic><topic>Circulating cytokines</topic><topic>Cluster Analysis</topic><topic>Cytokines - biosynthesis</topic><topic>Cytokines - blood</topic><topic>Ectopic germinal center</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Germinal Center - immunology</topic><topic>Germinal Center - pathology</topic><topic>Humans</topic><topic>Immunopathology</topic><topic>Medical sciences</topic><topic>Membrane Proteins - biosynthesis</topic><topic>Membrane Proteins - blood</topic><topic>Middle Aged</topic><topic>Multivariate Analysis</topic><topic>Salivary Gland Diseases - immunology</topic><topic>Salivary Glands, Minor - immunology</topic><topic>Sjogren's Syndrome - blood</topic><topic>Sjogren's Syndrome - immunology</topic><topic>Sjogren's Syndrome - pathology</topic><topic>Sjögren's syndrome</topic><topic>Tumor Necrosis Factor-alpha - biosynthesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Szodoray, Peter</creatorcontrib><creatorcontrib>Alex, Philip</creatorcontrib><creatorcontrib>Jonsson, Malin V.</creatorcontrib><creatorcontrib>Knowlton, Nicholas</creatorcontrib><creatorcontrib>Dozmorov, Igor</creatorcontrib><creatorcontrib>Nakken, Britt</creatorcontrib><creatorcontrib>Delaleu, Nicolas</creatorcontrib><creatorcontrib>Jonsson, Roland</creatorcontrib><creatorcontrib>Centola, Michael</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><jtitle>Clinical Immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Szodoray, Peter</au><au>Alex, Philip</au><au>Jonsson, Malin V.</au><au>Knowlton, Nicholas</au><au>Dozmorov, Igor</au><au>Nakken, Britt</au><au>Delaleu, Nicolas</au><au>Jonsson, Roland</au><au>Centola, Michael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Distinct profiles of Sjögren's syndrome patients with ectopic salivary gland germinal centers revealed by serum cytokines and BAFF</atitle><jtitle>Clinical Immunology</jtitle><addtitle>Clin Immunol</addtitle><date>2005-11-01</date><risdate>2005</risdate><volume>117</volume><issue>2</issue><spage>168</spage><epage>176</epage><pages>168-176</pages><issn>1521-6616</issn><eissn>1521-7035</eissn><eissn>1365-2567</eissn><coden>CLIIFY</coden><abstract>The formation of ectopic germinal centers (GC) has been described in Sjögren's syndrome (SS), although little is known about the molecular basis of this phenomenon. These structures are a focus of in situ autoantibody production and have been hypothesized to be involved in lymphomagenesis in SS patients. Serum cytokines also play an important role in SS pathogenesis in part via immune dysregulation and may therefore contribute to ectopic GC formation. Herein, highly multiplex cytokine screening of SS patients with (SSGC+) and without (SSGC−) GC formation was done to identify cytokine profiles that correlate with this phenomenon. Serum levels of B-cell activating factor (BAFF) were also screened as a potential biomarker of immune dysregulation in SS and SSGC formation. Univariate analysis demonstrated that serum levels of a broad spectrum of immune and inflammatory modulating cytokines are upregulated in SSGC+ and SSGC− patients relative to unaffected controls IL-1β, IL−2, IL-6, IL-15, IFN-γ and CCL4 (MIP-1β). SSGC+ patients were distinguished from healthy individuals by higher levels of IL-4, IL-10, GM-CSF, IFN-α, CCL3 (MIP-1α), CCL11 (Eotaxin) and BAFF, while SSGC+ and SSGC− patients differed in CCL2 (MCP-1) expression. Discriminant function analysis (DFA), a multivariate discrimination method that uses observed differences to characterize groups when casual relationships are not well understood, was employed to identify a subset of these biomarkers that maximally discriminate among SSGC+, SSGC− and unaffected individuals. The biomarker having the strongest discriminatory power identified by DFA besides CCL11 (Eotaxin) and IFN-γ was BAFF. The variables identified by DFA are interdependent and are often of mechanistic significance to the pathologic states they distinguish, suggesting that these factors modulate SS pathology and SSGC formation in a synergistic manner.</abstract><cop>San Diego, CA</cop><pub>Elsevier Inc</pub><pmid>16126006</pmid><doi>10.1016/j.clim.2005.06.016</doi><tpages>9</tpages></addata></record> |
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subjects | Adult B-Cell Activating Factor Biological and medical sciences Choristoma - immunology Circulating cytokines Cluster Analysis Cytokines - biosynthesis Cytokines - blood Ectopic germinal center Female Fundamental and applied biological sciences. Psychology Fundamental immunology Germinal Center - immunology Germinal Center - pathology Humans Immunopathology Medical sciences Membrane Proteins - biosynthesis Membrane Proteins - blood Middle Aged Multivariate Analysis Salivary Gland Diseases - immunology Salivary Glands, Minor - immunology Sjogren's Syndrome - blood Sjogren's Syndrome - immunology Sjogren's Syndrome - pathology Sjögren's syndrome Tumor Necrosis Factor-alpha - biosynthesis |
title | Distinct profiles of Sjögren's syndrome patients with ectopic salivary gland germinal centers revealed by serum cytokines and BAFF |
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