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GAD in Metabolic - Diamyd Medical AB

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More support for <strong>the</strong> autoimmune<strong>the</strong>ory came in <strong>the</strong> early1970’s when Dr. Bottazzo andDr. Doniach and colleagues at<strong>the</strong> Middlesex Hospital inLondon first detected <strong>anti</strong>bodiesto pancreatic islet cells in people <strong>with</strong> newly diagnoseddiabetes. The <strong>anti</strong>bodies, which react to <strong>the</strong> cytoplasminside all islet cells, came to be called cytoplasmicislet cell <strong>anti</strong>bodies or ICAs.Antibodies are a part of <strong>the</strong> immune system responsecalled <strong>the</strong> humoral response. Made by white blood cellscalled B lymphocytes, specific <strong>anti</strong>bodies are designed toattack specific foreign proteins or <strong>anti</strong>gens. It was unclear,however, whe<strong>the</strong>r <strong>the</strong> beta cells were actually destroyedby <strong>the</strong>se <strong>anti</strong>bodies or by components of <strong>the</strong> cellularimmune response, such as <strong>the</strong> killer T lymphocytes or“T cells”.In <strong>the</strong> mid-1970’s, Dr. Lernmark, who had developed atechnique for isolating beta cells from isolated islets of1990In a majorbreakthrough,scientistsidentify <strong>the</strong>64K proteinas <strong>GAD</strong>1991Scientistsdiscover that 64Kprotein is<strong>GAD</strong>65, <strong>the</strong>smaller formof <strong>GAD</strong>Study showsthat T cellstarget<strong>GAD</strong>651993Research teamsprevent diabetesin NOD mice byinactivating <strong>GAD</strong>-Reactive T cellsResearcherssuggest 64K<strong>anti</strong>bodies maybe earlypredictor ofdiabetesMolecularbiologistssequence twoforms of <strong>GAD</strong>– <strong>GAD</strong>65 and<strong>GAD</strong>67 – fromislet cellsStudies showthat someICAs only reactto <strong>GAD</strong>65Two studiesestablish <strong>GAD</strong>as first knowntarget of T cellsin diabeticNOD mice<strong>the</strong> Langerhans, was researching proteins on <strong>the</strong> surface ofbeta cells at <strong>the</strong> University of Chicago. While involved inthis research, he attended a lecture in ICAs in Chicago byDr. Doniach. During <strong>the</strong> lecture, he realized that it mustbe <strong>the</strong> proteins on <strong>the</strong> surface of <strong>the</strong> beta cells that provoked<strong>anti</strong>bodies in diabetes, and he turned his research inthat direction. He and o<strong>the</strong>r researchers at <strong>the</strong> Universityof Chicago treated pancreatic islets cells from rats <strong>with</strong>blood serum from children who had diabetes for less thanfive years. They discovered that some of <strong>the</strong>se childrenhad <strong>anti</strong>bodies to proteins on <strong>the</strong> surface of <strong>the</strong> islet cells,called islet cell surface <strong>anti</strong>bodies or ICAs. However, <strong>the</strong>ydid not know which specific proteins had attracted <strong>the</strong><strong>anti</strong>bodies.The 64,000 Mystery ProteinIn <strong>the</strong> late 1970’s, Dr. Lernmark became Director ofResearch at <strong>the</strong> Hagedorn Research Laboratory inDenmark, where he continued to work <strong>with</strong> ICAs. Heenlisted <strong>the</strong> aid of Dr. Baekkeskov, who had developeddmccad june 2003page 7

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