A product of immunoreactive trypsinogen and pancreatitis-associated protein as second-tier strategy in cystic fibrosis newborn screening

Sophia Weidler; Konrad H Stopsack; Jutta Hammermann; Olaf Sommerburg; Marcus A Mall; Georg F Hoffmann; Dirk Kohlmüller; Jürgen G Okun; Milan Macek Jr; Felix Votava; Veronika Krulišová; Miroslava Balaščaková; Veronika Skalická; Min Ae Lee-Kirsch; Marina Stopsack

doi:10.1016/j.jcf.2016.07.002

A product of immunoreactive trypsinogen and pancreatitis-associated protein as second-tier strategy in cystic fibrosis newborn screening

J Cyst Fibros. 2016 Nov;15(6):752-758. doi: 10.1016/j.jcf.2016.07.002. Epub 2016 Jul 22.

Authors

Affiliations

¹ Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany.
² Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
³ Division of Pediatric Pulmonology and Allergy and Cystic Fibrosis Center, Department of Pediatrics III, Children's Hospital, University of Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany.
⁴ Division of Pediatric Pulmonology and Allergy and Cystic Fibrosis Center, Department of Pediatrics III, Children's Hospital, University of Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany; Department of Translational Pulmonology, Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), University of Heidelberg, Im Neuenheimer Feld 156, D-69120 Heidelberg, Germany.
⁵ Department of General Pediatrics, Division of Metabolic Diseases and Newborn Screening Center, Department of Pediatrics I, Children's Hospital, University of Heidelberg, Im Neuenheimer Feld 430, D-69120 Heidelberg, Germany.
⁶ Department of Biology and Medical Genetics, 2nd Faculty of Medicine, Charles University Prague and Motol University Hospital, V Uvalu 84, Prague CZ 150 06, Czech Republic.
⁷ Department of Pediatrics, University Hospital Kralovske Vinohrady, 3rd Faculty of Medicine, Charles University, Srobarova 50, Prague, CZ 100 34, Czech Republic.
⁸ Department of Pediatrics, 2nd Faculty of Medicine, Charles University Prague and Motol University Hospital, V Uvalu 84, PragueCZ 150 06, Czech Republic.
⁹ Institute of Clinical Chemistry and Laboratory Medicine, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany. Electronic address: [email protected].

PMID: 27461140
DOI: 10.1016/j.jcf.2016.07.002

Abstract

Background: In cystic fibrosis newborn screening (CFNBS), immunoreactive trypsinogen (IRT) and pancreatitis-associated protein (PAP) can be used as screening parameters. We evaluated the IRT×PAP product as second-tier parameter in CFNBS in newborns with elevated IRT.

Methods: Data on 410,111 screened newborns including 78 patients with classical cystic fibrosis (CF) from two European centers were retrospectively analyzed by discrimination analysis to identify a screening protocol with optimal cutoffs. We also studied differences in PAP measurement methods and the association of IRT and PAP with age.

Results: PAP values differed systematically between fluorometric and photometric assays. The IRT×PAP product showed better discrimination for classical CF than PAP only as second-tier screening parameter (p<0.001). In CF patients, IRT decreased while PAP values remained high over years. In newborns without CF, IRT decreased after birth over weeks while PAP increased within days.

Conclusions: The IRT×PAP product performs well as second-tier cutoff parameter for CFNBS. Screening quality parameters depend on the analytic method and on age at blood collection.

Keywords: Cutoff; Cystic fibrosis; Immunoreactive trypsinogen; Newborn screening; Pancreatitis-associated protein.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Chemistry Techniques, Analytical
Cystic Fibrosis* / blood
Cystic Fibrosis* / diagnosis
Female
Humans
Infant, Newborn
Male
Neonatal Screening / methods*
Pancreatitis-Associated Proteins / analysis*
Retrospective Studies
Sensitivity and Specificity
Trypsinogen* / analysis
Trypsinogen* / immunology

Substances

Pancreatitis-Associated Proteins
Trypsinogen