CXCL13 is elevated in Sjögrenˈs syndrome in mice and humans and is implicated in disease pathogenesis

[摘要] SSisanautoimmunedisease.pSSaffectsexocrineglandspredominantly,whereassSSoccurswithotherautoimmuneconnectivetissuedisorders.Currently,careforpatientswithSSispalliative,asnoestablishedtherapeuticstargetthediseasedirectly,anditspathogeneticmechanismsremainuncertain.B‐cellabnormalitieshavebeenidentifiedinSS.CXCL13directsB‐cellchemotaxisandiselevatedinseveralautoimmunediseases.Inthisstudy,wetestedthehypothesisthatCXCL13iselevatedinSSinmiceandhumansandthatneutralizationofthechemokineamelioratesdiseaseinamurinemodel.WeassayedCXCL13inmousemodelsandhumansubjectswithSStodeterminewhetherCXCL13iselevatedbothlocallyandsystemicallyduringSSprogressionandwhetherCXCL13mayplayaroleinandbeabiomarkerforthedisease.Cxcl13expressioninsalivarytissueincreaseswithdiseaseprogression,anditsblockaderesultedinamodestreductioninglandularinflammationinanSSmodel.WedemonstratethatinhumansCXCL13iselevatedinserumandsaliva,andanelevatedsalivaryCXCL13leveldistinguishespatientswithxerostomia.ThesedatasuggestaroleforCXCL13asavaluablebiomarkerinSS,as74%ofpatientswithSSdisplayedelevatedCXCL13insera,saliva,orboth.Thus,CXCL13maybepathogenicallyinvolvedinSSandmayserveasanewmarkerandapotentialtherapeutictarget...

[学科分类] 生理学

[关键词] B‐cell;CXCR5;saliva;sialadenitis