Chemistry: analytical and immunological testing – For preexisting immune complex or auto-immune disease
Patent
1995-08-28
1998-03-03
Scheiner, Toni R.
Chemistry: analytical and immunological testing
For preexisting immune complex or auto-immune disease
436503, 435 721, 435 792, G01N 33531, G01N 33564, G01N 33567
Patent
active
057233438
ABSTRACT:
Acquired hypoparathyroidism (AH) occurs frequently as a component of type I autoimmune polyglandular disease (APS-I) or as a sporadic isolated disease in adults. Whereas autoantibodies to the parathyroid glands have been reported in AH, their very existence remains controversial. We report here the detection of autoantibodies as identified through immunoblotting using sera from AH patients. The antibodies were specific to parathyroid autoantigens obtained through differential centrifugation of fresh human hypercellular parathyroid glands, obtained shortly after their surgical removal for tertiary hyperparathyroidism in patients with renal failure. Autoantibodies were detected against several parathyroid specific proteins in the 17 AH sera tested. Twelve (70%) reacted to a protein of 70 kDa, while 16 (94%) reacted to a protein of 80 kDa, and 3 (18%) reacted to a protein of 120-140 kDa, respectively. The 70 and 80 kDa proteins were localized to the cytosolic fraction of the parathyroid extract, and the 120-140 kDa protein to the membrane fraction. The autoantibodies were also detectable using a dog parathyroid gland as an antigen source. However, they could not be identified using cultured human melanocytes or in rat pituitary cells as antigen sources. Sera from 50 patients with various other autoimmune diseases as well as 22 normal controls were also tested, and none reacted with any of the above specific parathyroid proteins. It is concluded that autoantibodies to 3 major autoantigens in the human parathyroid gland extract have been detected in AH patients. Furthermore, our data indicates that the 120-140 kDa autoantigen is the calcium sensing receptor and that the reactive epitope largely resides in its extracellular domain. These data confirm the autoimmune nature of AH, and the invention provides a method for detecting AH or propensity for AH as well as a method for treating AH.
REFERENCES:
patent: 4864020 (1989-09-01), Cance et al.
patent: 5053491 (1991-10-01), Cance et al.
Aurbach, G.D., S.J. Marx, A.M. Spiegel (1990) "Parathyroid Hormone, Calcitonin, and the Calciferols" Williams Textbook of Endorinology 8:1397-1476.
Neufeld, M., N. Maclaren, R. Blizzard (1980) "Autoimmune Polyglandular Syndrome" Pediatric Annals 9(4): 154-162.
Neufeld, M. N.K. Maclaren, R.M. Blizzard (1981) "Two Types of Autoimmune Addison's Disease Associated with Different Polyglandular Autoimmune (PGA) Syndrome" Medicine 60(5):355-362.
Winter, W. E., M. Obata, N.K. Maclaren (1992) "Clinical and Molecular Aspects of Autoimmune Endocrine Disease" Clinical and Molecular Aspects of Autoimmune Diseases. Concepts Immunopathol. 8:189-221.
Maclaren, N.K., W.J. Riley (1985) "Thyroid, Gastric and Adrenal Autoimmune Associated with Insulin-dependent Diabestes Melitus" Diabetes Care 8(1)34-38.
Muir, A., N.K. Maclaren (1991) "Autoimmune diseases of the Adrenal Glands, Parathyroid Glands, Gonads, and Hypothalamic-Pituitary Axis" Endocrinologly and Metabolism Clinics of North America 20(3):619-644.
Ahonen, P. et al. (1988) "The Expression Autoimmune Polyglandular Disease Type I Appears Associated with Several HLA-A Antigens but not with HLA-DR" Clinical Endocrinology and Metabolism 66(6)1152-1157.
Aaltonen, J. et al. (1994) "An autosomal locus causing autoimmune disease: autoimmune polyglandular disease type I assigned to chromosome 21" Nature Genetics 8:83-87.
Ahonen, P. et al. (1990) "Clinical Variation of Autoimmune Polyendocronopathy-Candidiasis-Ectodermal Dystrophy (Apeced) in a Series of 68 Patients" The New England Journal of Medicine 322(26):1829-1836.
Blizzzard, R.M. et al. (1996) "The Incidence of Parathyroid and other Antibodies in the Sera of Patients with Idiopathic Hypoparathyroidism" Clin. Exp. Immunol. 1:119-128.
Betterle, C. et al. (1985) "Demostration and characterization of anti-human mitochondria autoantibodies in idiopathic hypoparathyroism and in other conditions" Clin. exp. Immunol. 62:353-360.
Brandi, M.-L. et al. (1986). "Autoantibodies cytoxic to bovine parathyroid cells in autoimmune hypoparathyroidism" Proc. Natl. Acad. Sci. USA 83:8366-8369.
Fattorossi, A. et al. (1988) "Anti-endothelial cell natibodies: Detection and characterization in sera from patients with autoimmune hypoparathyroidism" Proc. Nat. Acad. Sci. USA 85:4015-4019.
Song, Y.-H. et al. (1995) "Acquired Hypoparathyroidism is Associated with Autoantibodies 70 and 80 KDa Parathyroid Specific Proteins as well as 120-140 KDa Calcium Receptor" 77th Annual Meeting of the Endocrine Society, Washington, D.C., Jun. 14-17, 1995, **abstract.
Pollak, M.R. et al. (1993) "Mutations in the Human Ca.sup.2+ -Sensing Receptor Gene Cause Familial Hypocalciuric Hypercalcemia and Neonatal Severe Hyperparathyroidism" Cell 75:1297-1303.
Brown, E.M. et al. (1993) "Cloning and characterization of an extracellular Ca.sup.2+ -sensing receptor from bovine parathyroid" Nature 366:575-580.
Irvine, W.J., L. Scarth (1969) "Antibody to the Oxyphil Cells of the Human Parathyroid in Idiopathic Hypoparathyroidism" Clin. exp. Immunol. 4:505-510.
Juhlin, C. et al. (1987) "Monoclonal antibodies with exclusive reactivity against parathyroid cells and tubule cells of the kidney" Proc. Natl. Acad. Sci. USA 84:2990-2994.
Wilkin, T.J. (1990) "Receptor Autoimmunity in Endocrine Disorders" The New England Journal of Medicine 323(19):1318-1324.
Davies, T.F. (1981) "Autoantibodies to the Human Thyrotropin Receptor Are Not Species Specific" Journal of Clincal Endocrinology and Metabolism 52:426-430.
Gonzalez-Ros, J.M. et al. (1984) "Binding of Anti-Acetylcholine Receptor Antibodies Inhibits the Acetylcholine Receptor Mdiatd Cation Flux" Biochemical and Biophysical Research Communications 120(2):368-375.
Fumagalli, G. et al. (1982) "Ultrastructural Aspects of Acetylcholine Receptor Turnover at the Normal End-plate and in Autoimmune Myasthenia Gravis" Journal of Neuropathology and Experimental Neurology 41(6):567-579.
Desouki, A. et al. (1981) "A New Mechanism Revealed for the Action of Antibodies on Acetylcholine Receptor Function" Experimental Neurology 73:440-450.
Loveridge, N. et al. (1980) "Inhibiton of parietal cell function by human gammaglobulin containing gastric parietal cell antibodies" Clin. exp. Immunol. 41:264-270.
Kendall-Taylor, P. et al. (1988) "Antibody that blocks stimulation of cortisol secretion by adrenocorticotrophic hormone in Addison's disease" British Medical Journal 296:1489-1491.
Maron, R. et al. (1983) "Autoantibodies to the receptor in juvenile onset insulin-dependent diabetes" Nature 303:817-818.
Wortsman, J. et al. (1992) "T-Lymphocyte Activation in Adult-Onset Idiopathic Hypoparathyroidism" The American Journal of Medicine 92:352-356.
Song, Y.-H. et al. (1994) "The role of tyrosinase in autoimmune vitiligo" The Lancet 344:1049-1052.
Leiser, M., L.M. Sherwood (1989) "Calcium-binding Proteins in the Parathyroid Gland" The Journal of Biological Chemistry 264(5):2792-2800.
Jones, K.H. et al. (1963) "Edetic-Acid Test of Parathyroid Insufficiency" The Lancet (Jul. 20, 1963):119-121..
Jones, K.H. et al. (1963) "Prevalence of Parathyroid Insufficiency after Thyroidectomy" The Lancet (Jul. 20, 1963):121-124.
Davis, R.H. et al. (1961) "Prevalence of Parathyroid Insufficiency after Thyroidectomy" The Lancet (Dec. 30, 1961):1432-1435.
Brown, E.M. (1991) "Extracellular Ca.sup.2+ and other Ions as Extracellular (First) Messengers" Biological Reviews 71(2):371-411.
Li, Yangxin, Yao-Hua Song, Nadeem Rais, Ellen Connor, Desmond Schatz, Andrew Muir, Noel Maclaren (1996) "Autoantibodies to the Extracellular Domain of the Calcium Sensoing Receptor in Patients with Acquired Hypoparathyroidism" J. Clin. Invest. 97(4):910-914.
Maclaren Noel K.
Song Yao-Huo
Bansal Geetha P.
Scheiner Toni R.
University of Florida
LandOfFree
Autoantibodies in patients with acquired hypoparathyroidism and does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Autoantibodies in patients with acquired hypoparathyroidism and , we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Autoantibodies in patients with acquired hypoparathyroidism and will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2246840