Development of an Assay for the Biomarker PIIINP

  • Objective: To develop a convenient, nonradiometric, and robust assay platform for the measurement of PIIINP.

    Performance Specification: Development of two different sets of antibody pairs with appropiate sensitivity and specificity for human PIIINP.

    Proposed Timeline: 24 weeks

    Description: PIIINP is the N-terminal pro-peptide of collagen type III. PIIINP is useful as a biomarker of liver fibrosis. Due to increased levels in serum in response to growth hormone administration, our client required a test for its detection. Outlined below are the major steps IBA took to accomplish this task:

    Purification of Bovine PIIINP

    9 kg of fetal calf skin were homogenized, extracted with 20 L salt solution, precipitated with ethanol, digested with enzyme and purified by ion exchange chromatography
    Purification of ~400,000 fold
    Characterization of the Bovine PIIINP

    Reducing SDS gels
    N-terminal sequence
    Bioequivalence to human PIINP was demonstrated using a commercial human PIIINP RIA
    Generation of Anti-PIIINP Antibodies.

    Epitope selection
    Monoclonal and polyclonal Ab’s produced
    Characterization of the anti-PIIINP antibodies by ELISA and Westerns blots
    Antibodies were evaluated for their ability to bind human PIIINP by RIA
    Development of an Assay

    Extensive pairing explored to obtain the best antibody pairs compared by sensitivity, selectivity etc.
    Optimiztion of selected antibody pairs (coating buffers, coating concentrations, biotinalyation of secondary antibodies, etc.)
    Optimization of standard curve
    Sample analysis and correlation to commercial ELISA

    Results: Very sensitive assay with a good sample correlation to the commercial RIA

  • Project Completion: 24 weeks