Sex differences in autoimmune diseases 英文参考文献.docVIP

VoskuhlBiologyofSexDifferences2011,2:1 /content/2/1/1 REVIEW OpenAccess Sexdifferencesinautoimmunediseases RhondaVoskuhl Abstract Womenaremoresusceptibletoavarietyofautoimmunediseasesincludingsystemiclupuserythematosus(SLE), multiplesclerosis(MS),primarybiliarycirrhosis,rheumatoidarthritisandHashimoto’sthyroiditis.Thisincreased susceptibilityinfemalescomparedtomalesisalsopresentinanimalmodelsofautoimmunediseasessuchas spontaneousSLEin(NZBxNZW)F1andNZM.2328mice,experimentalautoimmuneencephalomyelitis(EAE)inSJL mice,thyroiditis,Sjogren’ssyndromeinMRL/Mp-lpr/lprmiceanddiabetesinnon-obesediabeticmice.Indeed, beingfemaleconfersagreaterriskofdevelopingthesediseasesthananysinglegeneticorenvironmentalrisk factordiscoveredtodate.Understandinghowthestateofbeingfemalesoprofoundlyaffectsautoimmunedisease susceptibilitywouldaccomplishtwomajorgoals.First,itwouldleadtoaninsightintothemajorpathwaysof diseasepathogenesisand,secondly,itwouldlikelyleadtonoveltreatmentswhichwoulddisruptsuchpathways. Whystudysexdifferences? treatments.Incontrast,the‘besidetobenchtobedside’ Translationalresearchwhichstartswithaclinicalobser- approach begins with a clinical observation that is vation, such as the increased susceptibility to autoim- knowntobephysiologically relevant inthehumandis- munediseaseinfemales,canbetermedasa‘bedsideto ease.Forexample,inautoimmunedisease,amajordis- bench to bedside approach’. In contrast to the classic ease susceptibility factor isthestate ofbeing female. If ‘benchtobedside’approach,researchthatbeginswitha thiswereunderstood,onewouldhavediscoveredsome- clinical observation carries less inherent risk of failure. thingthatisindeedphysiologically significant. Inorder Inthe‘benchtobedside’approach,amoleculeofinter- tounderstand whybeing female confers increased sus- est is focused upon as a target to either block or ceptibility,onemustnextgotothebench,usinginvitro enhance because it isthought tobeeither disease pro- andinvivosystemstosi