SEROnegativemyastheniagravisisnolongerseronegative

Myastheniagravis(MG)iscausedbythefailureofneuromuscularsignaltransmissionandinthemajorityofpatientsthisiscausedbythepresenceofautoantibodiestotheacetylcholinereceptor(ARAbpositiveMGpatients).In10-20%ofthepatientswithgeneralizedMG,andinupto50%ofthepatientswithocularMGtheseautoantibodiescannotbedetected.InthesecasesthediseaseiscommonlyreferredtoasseronegativeMG(SNMG).ForalongtimetheseseronegativepatientsposedaseriouschallengeforadequatediagnosisofMG.

Recentstudiesshowedthepresenceofantibodiestothemuscle-specificreceptortyrosinekinase(MuSK)inseraofpatientswithgeneralizedseronegativeMG(inabout50%ofputativeseronegativeMGpatients).MuSKispartofanagrinreceptorcomplexandmediatestheagrin-inducedclusteringofacetylcholinereceptors.MuSKMGpatientsaremostlyfemale,haveprominentcranialandbulbarinvolvement,and(whencomparedtoARAbpositiveMGpatients)theonsetofthediseasetendstobeearlier(thirdorfourthdecade).ThemeasurementofMuSKantibodieswillsubstantiallyaiddiagnosisandclinicalmanagementofMG.

IBLInternationalMuSK-AbELISA

• Theworld’sfirstcommerciallyavailableELISAformeasuringMuSKautoantibodies
• Excellentclinicalsensitivityof95.8%andspecificityof100%
• Qualitative(cut-off)andquantitative(standardcurve)evaluationofresults
• High-performanceassay:lowcross-reactivity,goodlinearityandhighprecision

Clinicalindications

• SUSPectedmyastheniagravisinacetylcholinereceptorantibodynegativepatients
• Myastheniagravispatientswithatypicalclinicalpresentation(e.g.oropharyngealmyasthenia)
• PatientswithocularmyastheniagraviswillnotgenerallydevelopMuSKautoantibodies
• AnegativeMuSKantibodyteststilldoesnotruleoutadiagnosisofmyastheniagravis

MuSK-AbELISAissuperiortoonlycommerciallyavailableRIA

DataonthequalitativecomparisonofthemeasurementsofMuSKautoantibodiesin253serumsamplesshowthesuperiorityoftheIBLMuSK-AbELISAcomparedtotheonlycommerciallyavailableMuSK-AbRIA.

ExcerptfromtheInstructionsforUse

Myastheniagravis(MG)iscausedbythefailureofneuromusculartransmissionmediatedbyautoantibodies.About80to90%ofpatientswithgeneralizedMGhaveautoantibodiesagainstthemusclenicotinicacetylcholinereceptors.Theseantibodiescauselossofacetylcholinereceptornumbersandfunction,andleadtofailureofneuromusculartransmissionwithmuscleweakness.In10–20%ofpatientswithgeneralizedmyastheniagravisandinupto50%ofpatientswithocularmyastheniagravistherearenodetectableantibodiestotheacetylcholinereceptor.Insuchcasesthediseaseiscommonlyreferredtoasseronegativemyastheniagravis.Seronegativemyastheniagravishasbeenrecognizedasanantibodymediateddisease.Antibodiestomuscle-specificreceptortyrosinekinase(MuSK)weredemonstratedintheseraofpatientswithgeneralizedseronegativemyastheniagravis(inapproximately40%ofseronegativeMGpatients).MuSKispartofanagrinreceptorcomplexandmediatestheagrin-inducedclusteringofacetylcholinereceptorsduringsynapseformation,andisalsoexpressedatthematureneuromuscularjunction(NMJ).MuSKMGpatientsarepredominantlyfemale,haveprominentcranialandbulbarinvolvement,andtendtohaveahigherrateofcrisesthanthosewithotherformsofMG.Diseaseonsettendstobeearlier,withmostpatientspresentingbythethirdorfourthdecade.ThemeasurementofMuSKantibodieswillsubstantiallyaiddiagnosisandclinicalmanagementofMyastheniagravis.