Insulin-dependentdiabetesmellitus(IDDM)orTypeIDiabetesisadebilitatingchronicdiseasethatimpairsproductionandsecretionofthekeyhormoneinsulinandaltersbloodsugarmetabolism.InsulinissynthesisedandsecretedbypancreaticisletcellsorisletsofLangarhans.ThedisruptionofinsulinsynthesisiscausedbyimmunologicaldestructionoftheisletcellsbyautoantibodiesinIDDMpatients.Suchabnormalities(autoimmunity)maybegeneticallyinheritedand/ortriggeredbyexposuretotoxicchemicals,viralinfectionsandvariousformsofstress.IDDMhasacharacteristicasymptomaticprediabeticphasethatmaylastuptoseveralyears.Duringthisperiod,theaffectedindividualsexhibitthediminishingearly-phasereleaseofinsulininresponsetoanintravenous/oralglucosechallenge.Inthemajorityofcases,theseindividualscarrycirculatingisletcellautoantibodies(ICA)and/orinsulinautoantibodies(IAA).ICAcanbedetectedasearlyaseightyearspriortotheclinicalonsetofIDDMandthusmayserveasanearlyindicatorofthediseaseorofpredispositiontoit.IndividualswhoareICA-positivemayshowaprogressivelossoftheisletcellfunctionasindicatedbydisruptionoftheearly-phaseinsulinrelease.Whenthisearlyphaseinsulinreleasecompletelystops,clinicallyovertIDDMdevelops.ICAarepresentin70%ofpatientswithrecentonsetofIDDMcomparedwith0.1-0.5%ofthecontrolnon-diabeticpopulation.ICAarealsodetectedinfirstdegreerelativesofIDDMpatients.TheseindividualscomprisethesegmentofhumanpopulationwhoareatahighriskofdevelopingIDDM.SeveralstudiesreportedthattheICA-positivefirstdegreerelativesofIDDMpatientssubsequentlydevelopeddiabetes.OtherstudiesalsosuggestedthatthepresenceofserumICAandIAAisanindicatorortheenhancedlikelihoodtodevelopIDDM.Therefore,SEROlogicaldetectionofICAmaybeapowerfultoolforearlydiagnosisofIDDM.ThesignificanceoftheseautoantibodiesasMarkersofIDDMisalsoillustratedbytheirpresenceinnondiabeticindividualswhoultimatelydevelopIDDM.Riley,et.al.recentlyreportedthatdeterminationofICAinType2DiabetespatientscouldidentifyIDDMpriortotheonsetofclinicalsymptomsandpredicttheneedforinsulintherapy.Thus,thosepatientswhoareinitiallydiagnosedwithType2DiabetesandcarryserumICAmaydeterioratetoinsulindependence.EarlydetectionofcirculatingICAisimportanttoidentifytheindividualsinthegeneralpopulation,thesIBLingsandfamiliesofIDDMpatientswhoareatahigherriskofdevelopingthisdiseasebecauseoftheirgeneticpredispositiontodiabetes.AtarecentinternationalworkshoponICA,theimminentneedforanELISAtestforthedeterminationofisletcellautoimmunitywasemphasized.Currently,serumICAaredeterminedbyindirectimmunofluorescenceandhistochemicalmethodsemployingfrozenunfixedhuman/primateorratpancreaticsectionsassubstrates.Despitevariousattemptstoimproveandmodifythisproceduresinceitsoriginaldescriptionin1974,theindirectimmunoflourescence/histochemicaltechniquesuffersfrominherentmethodologicalproblems.Standardisationofthetechniquehasproventobeverydifficult.ThereliABIlityofthis"frozen-section"techniqueislimitedbyfactorssuchasthevariationfromonepancreastoanother,theinevitableneedforunfixedpancreatictissueandinfrequentavailabilityofthesuitabletissue.ThisICAtestisaqualitativeELISAtestforinvitrodetectionofcirculatingIgGantibodiesagainstpancreaticisletcellantigens.