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Cytokine and autoantibody profiling related to histopathological features in primary Sjögren's syndrome

Objective. To investigate a potential correlation between circulating cytokine and autoantibody levels and histopathological features in subgroups of patients with primary SS (pSS). Methods. Minor salivary gland biopsies from a cohort of 141 patients fulfilling the American–European consensus classi...

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Published in:Rheumatology (Oxford, England) England), 2009-09, Vol.48 (9), p.1102-1106
Main Authors: Reksten, Tove R., Jonsson, Malin V., Szyszko, Ewa A., Brun, Johan G., Jonsson, Roland, Brokstad, Karl A.
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description Objective. To investigate a potential correlation between circulating cytokine and autoantibody levels and histopathological features in subgroups of patients with primary SS (pSS). Methods. Minor salivary gland biopsies from a cohort of 141 patients fulfilling the American–European consensus classification criteria for pSS were re-examined and grouped according to focus score (FS) and germinal centre (GC) status; serum samples were analysed for autoantibodies, chemokines and cytokines. Results. Of the 115 available biopsies, 18 (16%) lacked characteristic focal mononuclear cell infiltrates [FS < 1 (FS−)] but patients were positive for Ro/SSA and/or La/SSB. IL-17, IL-1RA, IL-15, macrophage inflammatory protein (MIP)-1α, MIP-1β, eotaxin, IFN-α and IL-4 levels were significantly increased in the 27 (23%) patients with ectopic GC formation (GC+) in the salivary glands compared with the GC− patients (n = 70). In addition, minor differences in cytokine levels were found when comparing age groups. Conclusion. Degenerative changes observed in the minor salivary glands of patients with pSS may represent ‘burned out’ inflammation. The elevated levels of IL-4 found in these patients may influence the reduced salivary flow observed in GC+ patients. Increased titres of Th17-associated cytokines, IL-17, IL-1β and the IL-23 subunit IL-12p40, may indicate a higher activity of these cells in GC+ patients. Differences in cytokine levels may be utilized when sub-grouping the SS patients into disease phases and may consequently have implications for treatment.
doi_str_mv 10.1093/rheumatology/kep149
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To investigate a potential correlation between circulating cytokine and autoantibody levels and histopathological features in subgroups of patients with primary SS (pSS). Methods. Minor salivary gland biopsies from a cohort of 141 patients fulfilling the American–European consensus classification criteria for pSS were re-examined and grouped according to focus score (FS) and germinal centre (GC) status; serum samples were analysed for autoantibodies, chemokines and cytokines. Results. Of the 115 available biopsies, 18 (16%) lacked characteristic focal mononuclear cell infiltrates [FS &lt; 1 (FS−)] but patients were positive for Ro/SSA and/or La/SSB. IL-17, IL-1RA, IL-15, macrophage inflammatory protein (MIP)-1α, MIP-1β, eotaxin, IFN-α and IL-4 levels were significantly increased in the 27 (23%) patients with ectopic GC formation (GC+) in the salivary glands compared with the GC− patients (n = 70). In addition, minor differences in cytokine levels were found when comparing age groups. Conclusion. Degenerative changes observed in the minor salivary glands of patients with pSS may represent ‘burned out’ inflammation. The elevated levels of IL-4 found in these patients may influence the reduced salivary flow observed in GC+ patients. Increased titres of Th17-associated cytokines, IL-17, IL-1β and the IL-23 subunit IL-12p40, may indicate a higher activity of these cells in GC+ patients. Differences in cytokine levels may be utilized when sub-grouping the SS patients into disease phases and may consequently have implications for treatment.</description><identifier>ISSN: 1462-0324</identifier><identifier>EISSN: 1462-0332</identifier><identifier>DOI: 10.1093/rheumatology/kep149</identifier><identifier>PMID: 19574472</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Adiopocytes ; Adult ; Age Factors ; Age of Onset ; Atrophy ; Autoantibodies ; Autoantibodies - blood ; Autoantigens - immunology ; Biological and medical sciences ; Biopsy ; Cohort Studies ; Cytokines ; Cytokines - blood ; Degenerative changes ; Diseases of the osteoarticular system ; Fibrosis ; Germinal Center - pathology ; Humans ; Inflammation ; Medical sciences ; Middle Aged ; Ribonucleoproteins - immunology ; RNA, Small Cytoplasmic - immunology ; Salivary glands ; Salivary Glands, Minor - pathology ; Sarcoidosis. 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To investigate a potential correlation between circulating cytokine and autoantibody levels and histopathological features in subgroups of patients with primary SS (pSS). Methods. Minor salivary gland biopsies from a cohort of 141 patients fulfilling the American–European consensus classification criteria for pSS were re-examined and grouped according to focus score (FS) and germinal centre (GC) status; serum samples were analysed for autoantibodies, chemokines and cytokines. Results. Of the 115 available biopsies, 18 (16%) lacked characteristic focal mononuclear cell infiltrates [FS &lt; 1 (FS−)] but patients were positive for Ro/SSA and/or La/SSB. IL-17, IL-1RA, IL-15, macrophage inflammatory protein (MIP)-1α, MIP-1β, eotaxin, IFN-α and IL-4 levels were significantly increased in the 27 (23%) patients with ectopic GC formation (GC+) in the salivary glands compared with the GC− patients (n = 70). In addition, minor differences in cytokine levels were found when comparing age groups. Conclusion. Degenerative changes observed in the minor salivary glands of patients with pSS may represent ‘burned out’ inflammation. The elevated levels of IL-4 found in these patients may influence the reduced salivary flow observed in GC+ patients. Increased titres of Th17-associated cytokines, IL-17, IL-1β and the IL-23 subunit IL-12p40, may indicate a higher activity of these cells in GC+ patients. Differences in cytokine levels may be utilized when sub-grouping the SS patients into disease phases and may consequently have implications for treatment.</description><subject>Adiopocytes</subject><subject>Adult</subject><subject>Age Factors</subject><subject>Age of Onset</subject><subject>Atrophy</subject><subject>Autoantibodies</subject><subject>Autoantibodies - blood</subject><subject>Autoantigens - immunology</subject><subject>Biological and medical sciences</subject><subject>Biopsy</subject><subject>Cohort Studies</subject><subject>Cytokines</subject><subject>Cytokines - blood</subject><subject>Degenerative changes</subject><subject>Diseases of the osteoarticular system</subject><subject>Fibrosis</subject><subject>Germinal Center - pathology</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Ribonucleoproteins - immunology</subject><subject>RNA, Small Cytoplasmic - immunology</subject><subject>Salivary glands</subject><subject>Salivary Glands, Minor - pathology</subject><subject>Sarcoidosis. 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Vasculitis</topic><topic>Sjogren's Syndrome - immunology</topic><topic>Sjogren's Syndrome - pathology</topic><topic>SS-B Antigen</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Reksten, Tove R.</creatorcontrib><creatorcontrib>Jonsson, Malin V.</creatorcontrib><creatorcontrib>Szyszko, Ewa A.</creatorcontrib><creatorcontrib>Brun, Johan G.</creatorcontrib><creatorcontrib>Jonsson, Roland</creatorcontrib><creatorcontrib>Brokstad, Karl A.</creatorcontrib><collection>Istex</collection><collection>Open Access: Oxford University Press Open Journals</collection><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>MEDLINE - Academic</collection><jtitle>Rheumatology (Oxford, England)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Reksten, Tove R.</au><au>Jonsson, Malin V.</au><au>Szyszko, Ewa A.</au><au>Brun, Johan G.</au><au>Jonsson, Roland</au><au>Brokstad, Karl A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cytokine and autoantibody profiling related to histopathological features in primary Sjögren's syndrome</atitle><jtitle>Rheumatology (Oxford, England)</jtitle><addtitle>Rheumatology (Oxford)</addtitle><date>2009-09-01</date><risdate>2009</risdate><volume>48</volume><issue>9</issue><spage>1102</spage><epage>1106</epage><pages>1102-1106</pages><issn>1462-0324</issn><eissn>1462-0332</eissn><abstract>Objective. To investigate a potential correlation between circulating cytokine and autoantibody levels and histopathological features in subgroups of patients with primary SS (pSS). Methods. Minor salivary gland biopsies from a cohort of 141 patients fulfilling the American–European consensus classification criteria for pSS were re-examined and grouped according to focus score (FS) and germinal centre (GC) status; serum samples were analysed for autoantibodies, chemokines and cytokines. Results. Of the 115 available biopsies, 18 (16%) lacked characteristic focal mononuclear cell infiltrates [FS &lt; 1 (FS−)] but patients were positive for Ro/SSA and/or La/SSB. IL-17, IL-1RA, IL-15, macrophage inflammatory protein (MIP)-1α, MIP-1β, eotaxin, IFN-α and IL-4 levels were significantly increased in the 27 (23%) patients with ectopic GC formation (GC+) in the salivary glands compared with the GC− patients (n = 70). In addition, minor differences in cytokine levels were found when comparing age groups. 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subjects Adiopocytes
Adult
Age Factors
Age of Onset
Atrophy
Autoantibodies
Autoantibodies - blood
Autoantigens - immunology
Biological and medical sciences
Biopsy
Cohort Studies
Cytokines
Cytokines - blood
Degenerative changes
Diseases of the osteoarticular system
Fibrosis
Germinal Center - pathology
Humans
Inflammation
Medical sciences
Middle Aged
Ribonucleoproteins - immunology
RNA, Small Cytoplasmic - immunology
Salivary glands
Salivary Glands, Minor - pathology
Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis
Sjogren's Syndrome - immunology
Sjogren's Syndrome - pathology
SS-B Antigen
title Cytokine and autoantibody profiling related to histopathological features in primary Sjögren's syndrome
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