Neutrophil collagenase, gelatinase, and myeloperoxidase in tears of patients with stevens-johnson syndrome and ocular cicatricial pemphigoid.

Abstract

OBJECTIVE:

To investigate the levels of matrix metalloproteinases (MMPs), myeloperoxidase (MPO), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in tears of patients with Stevens-Johnson syndrome (SJS) and ocular cicatricial pemphigoid (OCP).

DESIGN:

Prospective, noninterventional cohort study.

PARTICIPANTS:

Four SJS patients (7 eyes), 19 OCP patients (37 eyes), and 20 healthy controls who underwent phacoemulsification (40 eyes).

METHODS:

Tear washes were collected from all patients and were analyzed for levels of MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, MPO, and TIMP-1 using multianalyte bead-based enzyme-linked immunosorbent assays. Total MMP activity was determined using a fluorometric assay. Correlation studies were performed between the various analytes within study groups.

MAIN OUTCOME MEASURES:

Levels of MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, MPO, and TIMP-1 (in nanograms per microgram of protein) and total MMP activity (in relative fluorescent units per minute per microgram of protein) in tears; MMP-8-to-TIMP-1 ratio; MMP-9-to-TIMP-1 ratio; and the correlations between MMP-8 and MMP-9 and both MMP and MPO.

RESULTS:

MMP-8, MMP-9, and MPO levels were elevated significantly in SJS and OCP tears (SJS>OCP) when compared with controls. The MMP activity was highest in SJS patients, whereas OCP patients and controls showed lower and similar activities. The TIMP-1 levels were decreased in SJS and OCP patients when compared with those in controls, with levels in OCP patients reaching significance. The MMP-8-to-TIMP-1 and MMP-9-to-TIMP-1 ratios were markedly elevated in SJS and OCP tears (SJS>OCP) when compared with those of controls. Across all study groups, MMP-9 levels correlated strongly with MMP-8 and MPO levels, and MMP-8 correlated with MPO, but it did not reach significance in SJS patients. There was no relationship between MMP-7 and MPO.

CONCLUSIONS:

Because MMP-8 and MPO are produced by inflammatory cells, particularly neutrophils, the correlation data indicate that they may be the common source of elevated enzymes, including MMP-9, in SJS and OCP tears. Elevated MMP-to-TIMP ratios and MMP activity suggest an imbalance in tear MMP regulation that may explain the predisposition of these patients to demonstrate corneal melting and chronic complications associated with persistent inflammation. Myeloperoxidase in tears may be a sensitive and specific marker for the quantification of ocular inflammation.

• Authors: Samer N Arafat, Ana M Suelves, Sandra Spurr-Michaud, James Chodosh, C Stephen Foster, Claes H Dohlman, Ilene K Gipson
• Journal: Ophthalmology (Ophthalmology) Vol. 121 Issue 1 Pg. 79-87 (Jan 2014) ISSN: 1549-4713 [Electronic] United States
• PMID: 23962653 (Publication Type: Journal Article)
• Copyright: Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Chemical References

• TIMP1 protein, human
• Tissue Inhibitor of Metalloproteinase-1
• Peroxidase
• Gelatinases
• Matrix Metalloproteinase 8

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Cohort Studies
• Enzyme-Linked Immunosorbent Assay
• Female
• Fluorometry
• Gelatinases (metabolism)
• Humans
• Male
• Matrix Metalloproteinase 8 (metabolism)
• Middle Aged
• Pemphigoid, Benign Mucous Membrane (enzymology)
• Peroxidase (metabolism)
• Prospective Studies
• Stevens-Johnson Syndrome (enzymology)
• Tears (enzymology)
• Tissue Inhibitor of Metalloproteinase-1 (metabolism)
• Young Adult