C-Reactive Protein (CRP) and Autoimmune Disease Facts and Conjectures英文文献资料.docVIP

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C-Reactive Protein (CRP) and Autoimmune Disease Facts and Conjectures英文文献资料.doc

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C-Reactive Protein (CRP) and Autoimmune Disease Facts and Conjectures英文文献资料

ClinicalDevelopmentalImmunology,September/December2004,Vol.11(3/4),pp.221–226 C-ReactiveProtein(CRP)andAutoimmuneDisease: FactsandConjectures ALEXANDERJ.SZALAI* DivisionofClinicalImmunologyandRheumatology,DepartmentofMedicine,TheUniversityofAlabamaatBirmingham,437BTinsleyHarrisonTower, 15303rdAvenueSouth,Birmingham,AL35294-0006USA C-reactiveprotein(CRP)isabloodcomponentcomprisedof?veidenticalsubunitswithacombined tt molecularmassof110kDa;inthepresenceofCa itbindsphosphocholine(PC)withhighaf?nity. Ligand-bound CRP activates complement and the protein reportedly binds various Fc receptors. Coincidentwithanowdecade-longresurgenceinclinicalinterestinassociationsofCRPwithdisease, ourlaboratoryhasbeeninvestigatingthebiologyofCRPinvivousinghumanCRPtransgenicmice (CRPtg).Atthattimewecon?rmedthatCRPaffectsahostdefensefunctionmediatedatleastinpart throughtheeliminationofpathogens.LessappreciatedandnotaswellunderstoodasCRP’sabilityto bind antigen and aid in the elimination of microbes, is its known ability to bind autoantigens and presumedcapacitytopromoteclearanceofapoptoticcells.TheselatterpropertiesofCRPhavelong beensuspectedtocontributetohomeostasisandtoautoimmunedisease.Inthisarticlewereviewand updatetheevidencegeneratedinCRPtgbyourgroupandinvitrobyothers’thatindicatesCRPismore thanjustanantimicrobialmoleculeandconvenientmarkerofin?ammation—rather,itprotectsagainst autoimmunity.Amechanistichypothesisispresentedtoaccountforthiscause-and-effectrelationship. Keywords: SLE;MS;In?ammation;Lupus;EAE;Apoptosis WHATISCRP? likelihoodandseverityofvariousin?ammatorydiseases, includingautoimmunity(Youngetal.,1991;Morrowand Ridker, 2000). Here we review and update evidence generatedbyourgroupandothers’thatindicatesCRPis more than just a convenient marker of in?ammation— rather, the association of CRP with autoimmune disease arises from underlying biology, i.e. cause-and-effect relationships.Ahypothesisisthenprofferedtoaccountfor theserelationships. C-reactiveprotein(CRP)isoneofonlytw