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
Hauptverfasser: Szodoray, Peter, Alex, Philip, Jonsson, Malin V., Knowlton, Nicholas, Dozmorov, Igor, Nakken, Britt, Delaleu, Nicolas, Jonsson, Roland, Centola, Michael
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container_end_page 176
container_issue 2
container_start_page 168
container_title Clinical Immunology
container_volume 117
creator Szodoray, Peter
Alex, Philip
Jonsson, Malin V.
Knowlton, Nicholas
Dozmorov, Igor
Nakken, Britt
Delaleu, Nicolas
Jonsson, Roland
Centola, Michael
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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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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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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source MEDLINE; Access via Wiley Online Library; IngentaConnect Free/Open Access Journals; Access via ScienceDirect (Elsevier); EZB-FREE-00999 freely available EZB journals; Wiley Online Library (Open Access Collection); PubMed Central
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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