Specificity of a Polyclonal Fecal Elastase ELISA for CELA3

PLoS One. 2016 Jul 26;11(7):e0159363. doi: 10.1371/journal.pone.0159363. eCollection 2016.

Abstract

Introduction: Elastase is a proteolytic pancreatic enzyme that passes through the gastrointestinal tract undergoing only limited degradation. ELISA tests to determine stool elastase concentrations have therefore been developed for the diagnosis of exocrine pancreatic insufficiency. Five different isoforms of pancreatic elastase (CELA1, CELA2A, CELA2B, CELA3A, CELA3B) are encoded in the human genome. We have investigated three different polyclonal antisera that are used in a commercial fecal elastase ELISA to determine their specificity for different pancreatic elastase isoforms.

Material and methods: Different polyclonal rabbit antisera against human elastase peptides (BIOSERV Diagnostics GmbH, Germany) were tested by Western blot analysis of human pancreatic juice, in HEK-293 cells expressing Elastase constructs, and in the protein content of porcine pancreatin, used for treatment of exocrine pancreatic insufficiency.

Results: In human pancreatic juice the polyclonal antisera detected proteins at the corresponding size of human pancreatic elastase isoforms (~29kDa). Transiently expressed GFP fusion protein of elastase isoform CELA3A (CELA3A-GFP), but not CELA2A (CELA2A-GFP) could be precipitated from HEK-293 cell lysates with the elastase antisera. We detected no cross-reactivity with elastases in the porcine pancreatic extracts (pancreatin) used for enzyme replacement therapy.

Conclusion: The polyclonal antisera used in a commercial fecal elastase ELISA are specific for the human pancreatic elastase isoform CELA3 and do not cross-react with elastase contained in pig pancreatin. While pancreatic elastase 1 (CELA1) is not expressed in the adult human pancreas, possible differences between the other isoforms regarding their cellular expression, pathophysiological role and relevance in exocrine pancreatic insufficiency deserve further investigation.

MeSH terms

  • Animals
  • Antibodies / immunology
  • Antibody Specificity / immunology
  • Cross Reactions / immunology
  • Enzyme Replacement Therapy
  • Enzyme-Linked Immunosorbent Assay*
  • Exocrine Pancreatic Insufficiency / diagnosis
  • Exocrine Pancreatic Insufficiency / enzymology
  • Exocrine Pancreatic Insufficiency / therapy
  • Feces / enzymology*
  • Humans
  • Pancreas / enzymology
  • Pancreas / metabolism
  • Pancreatic Elastase / immunology
  • Pancreatic Elastase / metabolism*
  • Protein Isoforms
  • Sensitivity and Specificity
  • Treatment Outcome

Substances

  • Antibodies
  • Protein Isoforms
  • CELA3A protein, human
  • Pancreatic Elastase

Grants and funding

Alfried-Krupp-von-Bohlen-und-Halbach-Foundation (Graduate Schools Tumour Biology and Free Radical Biology), Deutsche Krebshilfe/Dr. Mildred-Scheel-Stiftung (109102), Deutsche Forschungsgemeinschaft (DFG GRK840-E3/E4, Bundesministerium für Wirtschaft und Technologie (Pro Inno II KF0409001MD6), Bundesministerium für Bildung und Forschung (BMBF GANI-MED 03152061A and BMBF 0314107), European Union (EU-FP-7: EPC-TM and EU-FP7-REGPOT-2010-1) and EFRE-Fond in Mecklenburg Vorpommern (V-630-S-150-2012/132/133). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.