Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Patent
1995-10-10
1998-06-23
Hendricks, Keith D.
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
435 74, 435232, G01N 3353
Patent
active
057703817
DESCRIPTION:
BRIEF SUMMARY
This Application is a 371 of PCT/AU94/00056, filed Feb. 9, 1994.
FIELD OF THE INVENTION
This invention relates to methods for the identification of persons who have diabetes or a prediabetic status, and in particular it is directed to a diagnostic assay which will provide a simple and effective means of screening large populations of individuals to detect both diabetes and prediabetes (the early stages of diabetes prior to the onset of the clinical disease).
BACKGROUND OF THE INVENTION
Diabetes mellitus is a heterogeneous disorder. Insulin-dependent (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) are subtyped physiologically according to patients' dependence for survival on treatment with insulin.sup.1. IDDM is attributed to autoimmunity.sup.2 by reason of disease associations, autoantibodies to pancreatic islet cell antigens, similarities with animal models of IDDM and HLA linkages. The disease-relevant autoantigen or antigens in IDDM include a 64,000-M.sub.r protein demonstrable by immunoprecipitation from pancreatic islets.sup.3 but hitherto unidentified because of low abundance and assay difficulties. Immunoassay for antibody to the 64,000-M.sub.r antigen indicated that it was a specific marker for IDDM and preceded symptomatic onset of disease.sup.4. The recognition in cases of the Stiff Man syndrome of coexisting IDDM and a neural antigen of 64,000-65,000-M.sub.r identified as glutamic acid decarboxylase (GAD) led Baekkeskov et al..sup.5 to establish the coidentity of their 64,000-M.sub.r antigen and GAD. Recently, Rowley et al..sup.6 described a high frequency of positive results by radioimmunoprecipitation assay with IDDM sera and a GAD preparation from pig brain and proposed detection of antibodies to GAD as a useful diagnostic test as an autoimmune marker associated with IDDM.
Insulin-dependent diabetes mellitus is a frequently occurring disease that predominantly affects young individuals, less than age 15 years. The disease can, however, have an onset in early or even mid-adult life, hence there is a need for a test that has diagnostic and predictive capacity for IDDM in both childhood and in adult life. The disease itself, IDDM, occurs at highest frequencies in the developed and economically advanced communities in the world. There is a high incentive to diagnose IDDM at the earliest stage, and even in the preclinical stage before the disease can be recognised by conventional laboratory tests. The recognition of antibodies to GAD by a routinely applicable, sensitive and specific immunoassay kit would fulfil this need. Moreover, the need for early or preclinical recognition is heightened by the likelihood that specific immunotherapeutic procedures will be developed that will arrest the progress of islet cell destruction that underlies IDDM, noting that such procedures have already been applied successfully in a model in mice of IDDM. Arrest of the natural progression of IDDM could spare patients years of injections with insulin. The development and application of an efficient immunoassay for antibodies to GAD, as a diagnostic procedure for IDDM, would result in an estimated usage of an assay kit in numbers exceeding one million annually, worldwide.
Apart from this, 5-10% of adults presenting with diabetes are initially diagnosed as having the non-insulin dependent form (NIDDM), however, after aL period ranging from months to years, they convert to IDDM. These patients fall into a category called latent autoimmune diabetes in adults (LADA). It has been shown that 75-80% of this group of patients have detectable levels of antibodies, to GAD. It is likely that this test will become widely used to discriminate these patients at diagnosis, thus saving them from inappropriate therapy (i.e. diet and tablets) which could result in failure to control their diabetes with the subsequent risk of severe complications. Moreover, the test for antibodies to GAD could have predictive value if applied to individuals at risk by reason of genetic predisposition. The institution of insulin therapy
REFERENCES:
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D. L. Kaufman et al., "Autoimmunity to Two Forms of Glutamate Decarboxylase in Insulin-dependent Diabetes Mellitus", J. Clin. Invest., vol. 89, Jan. (1992), pp. 283-292.
Baekkeskov et al."Identification of the 64 K autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase," Nature 347:151-56 (1990).
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Mackay Ian Reay
Rowley Merrill Joy
Zimmet Paul Zev
Hendricks Keith D.
Monash University
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