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

Åke Lernmark, MD, Ph.D., and his colleagues atHagedorn Research Laboratory in Denmark, firstreported 64K proteins in humans in 1982.Steinunn Baekkeskov, Ph.D., played a primary role indetecting the 64K protein in humans and later worked incollaboration with Yale researchers to identify the proteinas GAD.Mark Atkinsson, Ph.D., and colleagues at the Universityof Florida in Gainesville, concluded in 1990 that 64Kautoantibodies might be the earliest and best marker fordiabetes yet identified.techniques for detecting membrane proteins while studyingthe role of antigens in African sleeping sickness. Usingnewly developed and very sensitive tests such as the“immunoprecipitation technique”, Drs. Baekkeskov,Lernmark and colleagues at the Hagedorn found 80-90percent of blood serum samples from children withnewly diagnosed diabetes had antibodies to an unidentifiedICSA with molecular weight of approximately 64,000daltons-or 64 kilodaltons. They dubbed the mystery protein64K, and reported their findings in 1982 in Nature.In 1984, they reported that 64K antibodies were oftenfound in diabetic BB rats (a commonly used animalmodel for human diabetes). One intriguing aspect of thisfinding was that the antibodies appeared 40 to 70 daysbefore the onset of diabetes. This suggested that the 64Kprotein was an early and major target of the immunesystem. But did this same predictive effect hold true forhumans as well?They next looked at blood serum samples of 14 peoplewho later developed diabetes. Eleven of them had antibodiesto the 64K protein - for up to seven years before theybegan to show symptoms of diabetes. This suggested that64K antibodies might be an early warning sign for theeventual development of diabetes.In the summer of 1986 Dr. Atkinson who had beenstudying environmental influences on diabetes in rats atthe University of Florida in Gainesville, traveled toHagedorn as a visiting scientist. There Baekkeskov taughthim the immunoprecipitation technique for detecting64K antibodies. Armed with this new skill, he returned tothe University of Florida, where he and Dr. NoelMaclaren, detected the 64K antibodies in nonobese diabetic(NOD) mice, a newly bred type of animal model fordiabetes. Finding the 64K antibodies in animals helpedconfirm that the 64K antigen was an important feature indiabetes.Drs. Atkinson, Maclaren, and colleagues also studiedfirst-degree relatives of people with diabetes, who were athigher risk for developing diabetes themselves. In 1990, inthe British Journal The Lancet, they reported finding 64Kautoantibodies in 23 of 28 people who developed diabetesup to seven years later. Based on these findings and thoseof the Hagedorn researchers they concluded that 64Kmight be the earliest and best marker for diabetes yetidentified and might be especially useful for predictingdiabetes.As diabetes researchers became increasingly aware ofhow important this protein was, they set out to analyzeits chemical characteristics to compare with known proteins.In 1988, Drs. Solimena, Camilli, and their colleagues atYale University reported in The New England Journal ofMedicine that they had found the target antigen in patientswith an autoimmune disorder called Stiff-ManSyndrome (“SMS”). SMS is a rare disorder of the centralnervous system in which a person’s muscles become moreand more rigid, and painful spasms occur. Patients withthe disorder were found to have antibodies to an enzymecalled Glutamic acid Decarboxylase, or GAD.GAD is responsible for converting the amino acid glutamateinto a protein called GABA, which the brain cells useto communicate. It turned out that many patients withpage 8 dmccad june 2003