A panel of 11 region-specific radioimmunoassays for measurements of human chromogranin A.
BACKGROUND
The primary structure of human chromogranin A (CgA) not only contains 10 pairs of basic amino acids, which are potential cleavage sites for specific endogenous proteases, but also other sites in the molecule can be subjected to cleavage. Several CgA-related peptides have been identified in tissue, and many of the biological effects attributed to CgA seem to be mediated by these peptides.


METHODS
Peptides homologous to defined parts of the human CgA molecule were selected and synthesised. Antibodies were raised, and 11 specific radioimmunoassays were developed. Plasma samples from 20 patients with neuroendocrine tumours were collected and measured in all assays.


RESULTS
All assays measured circulating levels of CgA-derived peptides. Only four of the assays measured concentrations that correlated with that of total CgA. However, concentrations of the individual CgA-related peptides were generally lower than the concentration of total CgA. Different neuroendocrine tumours seem to process CgA differently. The ratio between a given region-specific assay and total CgA is inversely correlated to tumour activity.


CONCLUSIONS
The assays presented allow measurements of defined regions of CgA and will thus become important tools for further studies of processing of CgA.
Stridsberg
Mats
M
Department of Medical Sciences, Clinical Chemistry, Uppsala University Hospital, S-751 85, Uppsala, Sweden. mats.stridsberg@akademiska.se
Eriksson
Barbro
B
Oberg
Kjell
K
Janson
Eva Tiensuu
ET
D000368:Aged; D000918:Antibody Specificity; D002276:Carcinoid Tumor / Q000097:blood / Q000737:chemistry; D053379:Chromogranin A; D002864:Chromogranins / Q000097:blood* / Q000737:chemistry; D004701:Endocrine Gland Neoplasms / Q000097:blood / Q000737:chemistry; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000097:blood*; D010190:Pancreatic Neoplasms / Q000097:blood / Q000737:chemistry; D019151:Peptide Library; D011863:Radioimmunoassay / Q000379:methods*
C506150:CHGA protein, human; D053379:Chromogranin A; D002864:Chromogranins; D019151:Peptide Library