Faculty Collaboration Database

Identification of molecular signatures of cystic fibrosis disease status with plasma-based functional genomics. Physiol Genomics 2019 Jan 01;51(1):27-41

Date

12/13/2018

Pubmed ID

30540547

Pubmed Central ID

PMC6383551

DOI

10.1152/physiolgenomics.00109.2018

Scopus ID

2-s2.0-85060056850 (requires institutional sign-in at Scopus site)   13 Citations

Abstract

Although cystic fibrosis (CF) is attributed to dysfunction of a single gene, the relationships between the abnormal gene product and the development of inflammation and progression of lung disease are not fully understood, which limits our ability to predict an individual patient's clinical course and treatment response. To better understand CF progression, we characterized the molecular signatures of CF disease status with plasma-based functional genomics. Peripheral blood mononuclear cells (PBMCs) from healthy donors were cultured with plasma samples from CF patients ( n = 103) and unrelated, healthy controls ( n = 31). Gene expression levels were measured with an Affymetrix microarray (GeneChip Human Genome U133 Plus 2.0). Peripheral blood samples from a subset of the CF patients ( n = 40) were immunophenotyped by flow cytometry, and the data were compared with historical data for age-matched healthy controls ( n = 351). Plasma samples from another subset of CF patients ( n = 56) and healthy controls ( n = 16) were analyzed by multiplex enzyme-linked immunosorbent assay (ELISA) for numerous cytokines and chemokines. Principal component analysis and hierarchical clustering of induced transcriptional data revealed disease-specific plasma-induced PBMC profiles. Among 1,094 differentially expressed probe sets, 51 genes were associated with pancreatic sufficient status, and 224 genes were associated with infection with Pseudomonas aeruginosa. The flow cytometry and ELISA data confirmed that various immune modulators are relevant contributors to the CF molecular signature. This study provides strong evidence for distinct molecular signatures among CF patients. An understanding of these molecular signatures may lead to unique molecular markers that will enable more personalized prognoses, individualized treatment plans, and rapid monitoring of treatment response.

Author List

Levy H, Jia S, Pan A, Zhang X, Kaldunski M, Nugent ML, Reske M, Feliciano RA, Quintero D, Renda MM, Woods KJ, Murkowski K, Johnson K, Verbsky J, Dasu T, Ideozu JE, McColley S, Quasney MW, Dahmer MK, Avner E, Farrell PM, Cannon CL, Jacob H, Simpson PM, Hessner MJ

Authors

Ellis D. Avner MD Professor in the Pediatrics department at Medical College of Wisconsin
Martin J. Hessner PhD Professor in the Pediatrics department at Medical College of Wisconsin
Amy Y. Pan PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin
Pippa M. Simpson PhD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin
James Verbsky MD, PhD Professor in the Pediatrics department at Medical College of Wisconsin
Katherine Woods in the CTSI department at Medical College of Wisconsin - CTSI

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Blood Donors
Case-Control Studies
Child
Child, Preschool
Cohort Studies
Cystic Fibrosis
Cystic Fibrosis Transmembrane Conductance Regulator
Cytokines
Female
Genotype
Humans
Immunophenotyping
Leukocytes, Mononuclear
Male
Middle Aged
Mutation
Neutrophils
Oligonucleotide Array Sequence Analysis
Plasma
Reactive Oxygen Species
Transcriptome
Young Adult