Diagnosis system for determining the biologically effective parathyroid hormone activity in a sample

Abstract

Diagnosis system or immunoassay for the determination of the effective parathyroid hormone activity in a sample, and for a diagnosis and treatment of calcium metabolism disturbances, osteopathies and hyper- or hypoparathyroidisms. The parathyroid hormone activity is measured with the aid of an antibody which binds to an epitope in the region of the receptor binding structure 15 to 22 of the parathyroid hormone, and an antibody which recognises whether the amino-terminal end 1 to 3 of the parathyroid hormone is intact. The assay permits the antagonistic characteristics of some parathyroid hormone fragments to be taken into account.

1 . Diagnosis system for the immunological determination of the effective human parathyroid hormone activity in a sample, the diagnostic system comprising
 a first antibody which specifically binds to an epitope between amino acids 15 to 22 of the human parathyroid hormone (SEQ ID NO:16) when added to the sample;   a second affinity-purified polyclonal antibody which binds to an epitope that is formed of the N-terminal amino acids 1-3 of the human parathyroid hormone (SEQ ID NO:16),   wherein the second antibody specifically binds human parathyroid hormone (SEQ ID NO:16) and substantially its biologically active fragments hPTH-1-32, hPTH-1-33, hPTH1-34, hPTH-1-37, hPTH1-38, hPTH1-84, hPTH-2-37, but does not bind to the biologically inactive fragments hPTH-3-37 or hPTH-4-37, when the binding of the second antibodies is effected in the presence of 0.05 to 0.1 weight percent of a mild detergent.   
     
     
         2 . Diagnosis system according to  claim 1 , which further comprises antibodies which specifically bind to the epitope between amino acids 4 to 14 of the human parathyroid hormone (SEQ ID NO:16) for determining the antagonistic activity when added to the sample. 
     
     
         3 . Diagnosis system according to  claim 2 , which further comprises antibodies which specifically bind to an epitope between amino acids 24 and 37 of the human parathyroid hormone (SEQ ID NO:16) for determining the antagonistic activity when added to the sample. 
     
     
         4 . Diagnosis system according to  claim 1  which is an immunoenzymetric assay. 
     
     
         5 . Diagnosis system as claimed in  claim 1  for use in the diagnosis and assessment of the degree of an hypo- or hyper-parathyroidism. 
     
     
         6 . Diagnosis system as claimed in  claim 1  for use in the determining the cause of disturbances to the calcium metabolism, osteopathies, kidney failure and diseases, which originate from a disturbed homeostasis of the calcium and phosphate contents of the blood.