Check GAD antibody positivity with the Diamyd anti-GAD RIA plate*

“our real excitement came from a thoroughly unexpected(and still unexplained) finding, that part of GAD65 showed astriking similarity to a piece of Coxsackievirus, a virus”that isepidemiologically associated with Type 1 diabeteseffective diagnostic or predictive test for T1D.While autoantibodies are hallmarks of the autoimmuneprocess and are valuable prediagnosticmarkers, autoreactive T cells, rather than autoantibodies,are likely to be the underlying cause ofT1D. In further collaboration with Maclaren andAtkinson, we showed that newly diagnosed T1Dpatients, in contrast to healthy controls, have significantT cell responses to purified recombinanthuman GAD65.We knew that these discoveries would be usefuland important, but our real excitement came froma thoroughly unexpected finding – that part ofGAD65 showed a striking similarity to a piece ofCoxsackie virus a virus that is epidemiologicallyassociated with T1D. This sequence match sugggesteda possible mechanism for the initiation ofan immune response. We thought that T1D mightinvolve “molecular mimicry,” in which theCoxsackie viral antigen triggered an immuneresponse that cross-reacted with GAD. With thishighly speculative hypothesis of molecular mimicryin mind, we set about to look for evidencethat GAD autoimmunity might actually be pathogenicrather than merely diagnostic in T1D.To test the hypothesis that an autoimmuneresponse toGAD65 initiatesautoimmunity,DanKaufman andour otherUCLA colleaguesturned tothe non-obesediabetic mouse(NOD mice).Allan Tobin, Ph.D., is aProfessor and Directorof the Brain ResearchInstitute at UCLA, LosAngeles. Tobin is alsoScientific Director of theHereditary DiseaseFoundation, which participatedin the identification of the gene thatcauses Huntington´s disease. Tobin has specializedin the use of molecular methods for synthesis,function and breaking down of GABA.GABA provides a significant inhibitory signal inthe brain and the pancreas.Early treatment with GAD65 induced tolerancenot only to GAD65 itself, as expected, but alsoprevented the development of autoimmunity toother ß cell antigens as well.Still more amazingly, mice made tolerant toGAD65 never developed insulitis or diabetes. Thiswas our first strong indication that GAD-specificautoimmunity may be important in the pathogenesisof T1D. This finding, together with subsequentwork by Dan Kaufman and others, was thebasis for the clinical trial now being conductedby diamyd medical.dmccad june 2003page 15