title: Elevated Neutrophil Elastase in Tears of Ocular Graft-Versus-Host Disease Patients.
abstract: OBJECTIVE
  To investigate the levels of neutrophil elastase (NE), matrix metalloproteinases (MMPs), and myeloperoxidase (MPO) in tear washes of patients with ocular graft-vs-host disease (oGVHD).
  
  
  METHODS
  Case-control study.
  
  
  METHODS
  Based on established criteria, oGVHD patients (n = 14; 28 eyes) and age-/sex-matched healthy controls (n = 14; 28 eyes) were enrolled. Tear washes were collected and analyzed for NE using a single-analyte enzyme-linked immunosorbent assay (ELISA). MMPs (1, 2, 3, 7, 8, 9, 12), MPO, and tissue inhibitor of matrix metalloproteinase (TIMP)-1 were analyzed using multianalyte bead-based ELISA assays. Total MMP activity was measured using a fluorimetric assay. Correlation studies were performed between NE, MMP-8, MMP-9, and MPO within study groups.
  
  
  RESULTS
  NE, MMP-8, MMP-9, and MPO levels were elevated in oGVHD tears when compared with controls (P < .0001). NE was the most elevated analyte. MMP activity was higher and TIMP-1 levels were lower in oGVHD than in control (P < .0001). In oGVHD, NE significantly correlated with MMP-8 (r = 0.92), MMP-9 (r = 0.90), and MPO (r = 0.79) (P < .0001). MMP-8 correlated with MMP-9 (r = 0.96, P < .0001), and MPO (r = 0.60, P = .001). MMP-9 correlated with MPO (r = 0.55, P = .002). In controls, NE, MMP-9, and MPO significantly correlated with each other (P < .0001).
  
  
  CONCLUSIONS
  The marked increase in NE in oGVHD tears that correlated strongly with elevated MMP-8, MMP-9, and MPO suggests a common neutrophilic source and provides evidence of neutrophil activity on the ocular surface of oGVHD patients.
authors.affiliation: Schepens Eye Research Institute-Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts; Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts.
authors.forename: Samer N
authors.initials: SN
authors.lastname: Arafat
authors.affiliation: Schepens Eye Research Institute-Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts; Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Robert
authors.affiliation: Schepens Eye Research Institute-Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts; Department of Ophthalmology and Visual Sciences, Paulista School of Medicine, Federal University of Sao Paulo-UNIFESP, Sao Paulo, Brazil.
authors.forename: Tulio
authors.initials: T
authors.lastname: Abud
authors.affiliation: Schepens Eye Research Institute-Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts.
authors.forename: Sandra
authors.initials: S
authors.lastname: Spurr-Michaud
authors.affiliation: Schepens Eye Research Institute-Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts; Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts.
authors.forename: Francisco
authors.initials: F
authors.lastname: Amparo
authors.affiliation: Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts.
authors.forename: Claes H
authors.initials: CH
authors.lastname: Dohlman
authors.affiliation: Schepens Eye Research Institute-Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts; Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts.
authors.forename: Reza
authors.initials: R
authors.lastname: Dana
authors.affiliation: Schepens Eye Research Institute-Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts. Electronic address: ilene_gipson@meei.harvard.edu.
authors.forename: Ilene K
authors.initials: IK
authors.lastname: Gipson
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000201:enzymology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D013666:Tears / Q000201:enzymology*
chemical_list: D015415:Biomarkers; D019272:Leukocyte Elastase