title: Correlations of salivary biomarkers with clinical assessments in patients with cystic fibrosis.
abstract: BACKGROUND
  Monitoring clinical disease status in cystic fibrosis frequently requires invasive collection of clinical samples. Due to its noninvasive collection process and direct anatomic relationship with the lower airway, saliva shows great potential as a biological fluid for cystic fibrosis monitoring.
  
  
  OBJECTIVE
  To measure the levels of multiple protein markers in human saliva supernatants and investigate the possibility of utilizing them to provide a more quantitative measure of disease state for use in research and monitoring of patients with cystic fibrosis clinically.
  
  
  METHODS
  Whole saliva samples were collected and processed from cystic fibrosis patients at two distinct time points (2010 and 2013) and measured by two separate platforms. In this cross sectional study, a convenience sample of 71 participants were recruited with samples measured by multiplexed fluorescence microarray (fiber microarray) and another 117 participant samples were measured by an automated, point-of-care, analyzer (SDReader) using a microsphere-based array via fluorescence sandwich immunoassay. For comparison, saliva from 56 and 50 healthy subjects were collected, respectively. The levels of six target proteins were quantified. Various demographic and clinical data, including spirometry, medical history, and clinicians' assessments were also collected from patients with cystic fibrosis on the day of saliva collection.
  
  
  RESULTS
  Similar trends were observed with both platforms and compared with healthy subjects, cystic fibrosis patients had significantly elevated levels of VEGF, IP-10, IL-8, and EGF as well as lower levels of MMP-9 (P ≤ 0.005) using fiber microarray and significantly elevated levels of IP-10, IL-8 with lower levels of MMP-9 and IL-1β (P ≤ 0.02) using the SDReader. The levels of the six proteins correlated with each other significantly, and in some cases, biomarker levels could be used to differentiate between subgroups of patients with different clinical presentations. For example, IP-10 levels significantly correlated with FEV1 and disease severity (as evaluated by clinicians) with both platforms (P < 0.05).
  
  
  CONCLUSIONS
  Significant variations of the levels of six proteins in saliva supernatants, and the correlations of these levels with clinical assessments, demonstrated the potential of saliva for cystic fibrosis research and monitoring.
authors.affiliation: Department of Chemistry, Tufts University, Medford, Massachusetts, United States of America.
authors.forename: Shuai
authors.initials: S
authors.lastname: Nie
authors.affiliation: Department of Chemistry, Tufts University, Medford, Massachusetts, United States of America.
authors.forename: Huaibin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Chemistry, Tufts University, Medford, Massachusetts, United States of America.
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Mayer
authors.affiliation: Goldman School of Dental Medicine, Boston University, Boston, Massachusetts, United States of America.
authors.forename: Frank G
authors.initials: FG
authors.lastname: Oppenheim
authors.affiliation: School of Medicine, Boston University, Boston, Massachusetts, United States of America.
authors.forename: Frédéric F
authors.initials: FF
authors.lastname: Little
authors.affiliation: Division of Respiratory Diseases, Boston Children's Hospital and Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Greenberg
authors.affiliation: Division of Respiratory Diseases, Boston Children's Hospital and Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Ahmet Z
authors.initials: AZ
authors.lastname: Uluer
authors.affiliation: Department of Chemistry, Tufts University, Medford, Massachusetts, United States of America.
authors.forename: David R
authors.initials: DR
authors.lastname: Walt
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000378:metabolism*; D002648:Child; D003430:Cross-Sectional Studies; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology*; D004815:Epidermal Growth Factor / Q000378:metabolism*; D005260:Female; D006801:Humans; D007118:Immunoassay; D016209:Interleukin-8 / Q000378:metabolism*; D008137:Longitudinal Studies; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D040081:Protein Array Analysis; D012129:Respiratory Function Tests; D012463:Saliva / Q000737:chemistry; D013147:Spirometry; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D016209:Interleukin-8; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D004815:Epidermal Growth Factor; D020780:Matrix Metalloproteinase 9