Antibodies against Human Cytomegalovirus in the Pathogenesis of Systemic Sclerosis A Gene Array Approach 英文参考文献.docVIP

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Antibodies against Human Cytomegalovirus in the Pathogenesis of Systemic Sclerosis A Gene Array Approach 英文参考文献.doc

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Antibodies against Human Cytomegalovirus in the Pathogenesis of Systemic Sclerosis A Gene Array Approach 英文参考文献

o PL S MEDICINE AntibodiesagainstHumanCytomegalovirus inthePathogenesisofSystemicSclerosis: AGeneArrayApproach Claudio Lunardi1*,Marzia Dolcino2,Dimitri Peterlana1,Caterina Bason1,Riccardo Navone1,Nicola Tamassia3, Ruggero Beri1,Roberto Corrocher1,Antonio Puccetti2,4 1 Department of Clinical and Experimental Medicine, Section of Internal Medicine, University of Verona, Verona, Italy, 2 Institute Giannina Gaslini, Genova, Italy, 3DepartmentofPathology,SectionofGeneralPathology,UniversityofVerona,Verona,Italy,4DepartmentofExperimentalMedicine,SectionofHistology,Universityof Genova,Genova,Italy CompetingInterests:Theauthors havedeclaredthatnocompeting interestsexist. ABSTRACT Background AuthorContributions:CLandAP conceivedtheideaandwerethe principalinvestigatorsoftheGenova andVeronateams,respectively.MD andDPperformedtheanalysisofall thegenesup-anddownregulated. CBwasresponsibleforcellcultures andpurificationoftheantibodies. RNperformedtheWesternblotting andhelpedintheanalysisofthe genes.NTperformedthereal-time quantitativePCR.RBmeasuredthe solublemoleculesinthepatients’ andcontrols’sera.RCadvisedonthe preparationofthereport.CLandAP wrotethearticle,withinputfrom DP. Systemicsclerosisisanautoimmunediseasecharacterizedbyimmunologicalabnormalities, vascular damage, and fibroblast proliferation. We have previously shown that a molecular mimicrymechanismlinksantibodiesagainstthehuman-cytomegalovirus-derivedproteinUL94 tothe pathogenesis ofsystemic sclerosis. The UL94 epitope shows homology with NAG-2, a surfacemoleculehighlyexpressedonendothelialcells.Anti-UL94peptideantibodiespurified from patients’ sera induce apoptosis of endothelial cells upon engagement of the NAG-2– integrincomplex. MethodsandFindings WeshowherethatNAG-2isexpressedondermalfibroblastsandthatanti-UL94antibodies bind to fibroblasts. We have used the gene array strategy (Affimetrix oligonucleotide microarrays) to analyze the transcriptional profile in response to a 4-h and an 8-h treatment withantibo