Increased C-Peptide Immunoreactivity in Insulin Autoimmune Syndrome (Hirata Disease) Due to High Molecular Weight Proinsulin.
BACKGROUND: Determination of C-peptide is important in the investigation of unexplained hyper insulinemic hypoglycemia because a high C-peptide concentration usually indicates endogenous insulin hypersecretion. Insulin autoimmune syndrome (IAS) denotes hyper insulinemic hypoglycemia due to insulin-b...
| Published in: | Clinical Chemistry Vol. 67; no. 6; pp. 854 - 863 |
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| Main Authors: | , , , , , , , , |
| Format: | Journal Article |
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Oxford University Press / USA
Jun2021
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=151311605&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 151311605 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00099147 10CS jtl: Clinical Chemistry issn: 00099147 maglogo: N pubinfo: dt: Jun2021 vid: 67 iid: 6 pid: 622 pub: Oxford University Press / USA artinfo: ui: 151311605 10.1093/clinchem/hvab043 151311605 ppf: 854 ppct: 9 formats: fmt: @attributes: type: P tig: atl: Increased C-Peptide Immunoreactivity in Insulin Autoimmune Syndrome (Hirata Disease) Due to High Molecular Weight Proinsulin. aug: au: Kay, Richard G. Barker, Peter Burling, Keith Cohen, Mark Halsall, David Reimann, Frank Gribble, Fiona M. Semple, Robert K. Church, David affil: University of Cambridge Metabolic Research Laboratories, Wellcome Trust–MRC Institute of Metabolic Science, Cambridge, UK. sug: ab: BACKGROUND: Determination of C-peptide is important in the investigation of unexplained hyper insulinemic hypoglycemia because a high C-peptide concentration usually indicates endogenous insulin hypersecretion. Insulin autoimmune syndrome (IAS) denotes hyper insulinemic hypoglycemia due to insulin-binding antibodies that prolong insulin half-life. C-peptide clearance is considered to be unaffected, and although a marked C-peptide immunoreactivity in hypoglycemic samples has been reported, it has been suspected to be artifactual. High-resolution mass spectrometry enables examination of the basis of C-peptide-immunoreactivity in IAS. METHODS: Precipitation of plasma with polyethylene glycol was followed by C-peptide immunoassay. Plasma peptides extracted by solvent precipitation were characterized by nano-LC–MS/MS and analyzed using an untargeted data-dependent method. Peptides related to proinsulin, in amino acid sequence, were identified using proprietary bioinformatics software and confirmed by repeat LC– MS/MS analysis. Gel filtration chromatography coupled to LC–MS/MS was used to identify proinsulin-related peptides present in IAS immunocomplexes. Results were compared with those from C-peptide immunoassay. RESULTS: Polyethylene glycol precipitation of IAS plasma, but not control plasma, depleted C-peptide immunoreactivity consistent with immunoglobulin-bound C-peptide immunoreactivity. LC–MS/MS detected proinsulin and des 31,32 proinsulin at higher abundance in IAS plasma compared with control plasma. Analysis by gel filtration chromatography coupled to LC–MS/MS demonstrated proinsulin and des 31,32 proinsulin, but no C-peptide, in plasma immunocomplexes. CONCLUSIONS: Antibody binding can enrich proinsulin and des 31,32 proinsulin in IAS immunocomplexes. Proinsulin cross-reactivity in some C-peptide immunoassays can lead to artifactually increased C-peptide results. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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