Newborn Screening for Cystic Fibrosis by Use of a Multiplex Immunoassay

Overview

Journal Clin Chem

Publisher Oxford University Press

Specialty Biochemistry

Date 2009 Dec 31

PMID 20040620

Citations 5

Authors

Barbara A Lindau-Shepard

Kenneth A Pass

Affiliations

Soon will be listed here.

Abstract

Background: Since its beginnings, newborn screening for cystic fibrosis (CF) using an assay for immunoreactive trypsinogen (IRT) has been plagued by a high rate of false-positive results (screen positive, diagnosis negative), despite attempts to reduce this rate by use of altered cutoffs and second-tier DNA testing. IRT exists as 2 isoforms: IRT1 and IRT2, with IRT2 being more closely aligned with pancreatic disease, including CF. Assay standardization between programs is a continuing problem because the IRT assays currently in use variously recognize either 1 or both isoforms. Here we report the development of a multiplexed assay for both forms of IRT simultaneously.

Methods: Using 2 different Luminex bead sets, we developed assays for each IRT isoform separately and then combined them. Using the sum of IRT1 and IRT2 values (IRT1+IRT2), we compared the results with a CF kit currently in use.

Results: In a sample set consisting of 16 cases confirmed positive for CF, we established a cutoff at >97 microg/L total IRT. Seven of 8 carriers with 1 CF mutation screen-positive by the standard method were also screen-positive by IRT1+IRT2. Of 32 cases screen-positive by standard IRT, 11 were screen-negative by IRT1+IRT2. None of these 11 cases had CF mutations identified by the screening program.

Conclusions: These data indicate that the multiplex method with specificity for 2 isoforms of IRT has performance comparable to that of a standard IRT method and the advantage of improved standardization by detection of the 2 isoforms.

Citing Articles

Variants in Solute Carrier SLC26A9 Modify Prenatal Exocrine Pancreatic Damage in Cystic Fibrosis.

Miller M, Soave D, Li W, Gong J, Pace R, Boelle P J Pediatr. 2015; 166(5):1152-1157.e6.

PMID: 25771386 PMC: 4530786. DOI: 10.1016/j.jpeds.2015.01.044.

Newborn screening for autism: in search of candidate biomarkers.

Mizejewski G, Lindau-Shepard B, Pass K Biomark Med. 2013; 7(2):247-60.

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Multiplex method for simultaneous serological detection of porcine reproductive and respiratory syndrome virus and porcine circovirus type 2.

Lin K, Wang C, Murtaugh M, Ramamoorthy S J Clin Microbiol. 2011; 49(9):3184-90.

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A multiplex immunoassay using the Guthrie specimen to detect T-cell deficiencies including severe combined immunodeficiency disease.

Janik D, Lindau-Shepard B, Marie Comeau A, Pass K Clin Chem. 2010; 56(9):1460-5.

PMID: 20660143 PMC: 3220183. DOI: 10.1373/clinchem.2010.144329.

Frequency of Usher syndrome in two pediatric populations: Implications for genetic screening of deaf and hard of hearing children.

Kimberling W, Hildebrand M, Shearer A, Jensen M, Halder J, Trzupek K Genet Med. 2010; 12(8):512-6.

PMID: 20613545 PMC: 3131500. DOI: 10.1097/GIM.0b013e3181e5afb8.

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