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Conjunctival Matrix Metalloproteinase-9 Clinical Assessment in Early Ocular Graft versus Host Disease

PURPOSE: Graft versus Host Disease (GVHD) typically affects the ocular surface, with a presentation resembling Dry Eye Disease (DED). Although the etiopathology is not completely known, the conjunctiva might be a key site of T-cell activation. The differential diagnosis might be tricky at early stag...

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Autores principales: Berchicci, Luigi, Aragona, Emanuela, Arrigo, Alessandro, Marchese, Alessandro, Miserocchi, Elisabetta, Bandello, Francesco, Modorati, Giulio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216819/
https://www.ncbi.nlm.nih.gov/pubmed/34234963
http://dx.doi.org/10.1155/2021/9958713
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author Berchicci, Luigi
Aragona, Emanuela
Arrigo, Alessandro
Marchese, Alessandro
Miserocchi, Elisabetta
Bandello, Francesco
Modorati, Giulio
author_facet Berchicci, Luigi
Aragona, Emanuela
Arrigo, Alessandro
Marchese, Alessandro
Miserocchi, Elisabetta
Bandello, Francesco
Modorati, Giulio
author_sort Berchicci, Luigi
collection PubMed
description PURPOSE: Graft versus Host Disease (GVHD) typically affects the ocular surface, with a presentation resembling Dry Eye Disease (DED). Although the etiopathology is not completely known, the conjunctiva might be a key site of T-cell activation. The differential diagnosis might be tricky at early stages, because of the lack of dedicated clinical and laboratory tests. To meet these needs, we evaluated the suitability of ocular surface matrix metalloproteinase-9 (MMP-9) clinical test. METHODS: Consecutive GVHD patients, referred to IRCCS San Raffaele Scientific Institute, were recruited. DED patients served as controls. MMP-9 was tested through InflammaDry immunoassay kit in both groups; Ocular Surface Disease Index (OSDI) questionnaire, tear osmolarity, fluorescein Tear Break-up Time (TBUT), corneal and conjunctival staining, and Schirmer test I were also collected. Parametric and nonparametric statistical tests were used to analyze the intergroup differences; Receiver Operating Characteristics (ROC) curve analysis was carried out to perform sensitivity and specificity evaluations. RESULTS: Forty-five GVHD and 40 DED patients were included. MMP-9 expression was significantly higher in GVHD group than in DED (84.4% vs 33%, p ≤ 0.001). Corneal and conjunctival staining scores resulted worse in GVHD than in DED (0.95 ± 1.16 vs 0.40 ± 0.63, p=0.02; 0.77 ± 0.42 vs 0.40 ± 0.49, p=0.0005, respectively). No significant differences regarded the other collected parameters. GVHD group was characterized by positive correlations between MMP-9 and conjunctival staining (rho = 0.55, p=0.0002) and between MMP-9 and OSDI (rho = 0.3, p=0.01); a faint inverse correlation was found between MMP-9 and Schirmer test (rho = −0.25, p=0.04). CONCLUSION: MMP-9 has a role in physiologic cellular remodeling; when a proinflammatory stimulus occurs, MMP-9 molecules are overreleased in the extracellular matrix. The positive expression of MMP-9 in GVHD may be interpreted as the consequence of a T-cell aggression against self-antigens and may be considered a reliable biomarker to detect ocular surface inflammation in GVHD, even in early stages of the disease.
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spelling pubmed-82168192021-07-06 Conjunctival Matrix Metalloproteinase-9 Clinical Assessment in Early Ocular Graft versus Host Disease Berchicci, Luigi Aragona, Emanuela Arrigo, Alessandro Marchese, Alessandro Miserocchi, Elisabetta Bandello, Francesco Modorati, Giulio J Ophthalmol Research Article PURPOSE: Graft versus Host Disease (GVHD) typically affects the ocular surface, with a presentation resembling Dry Eye Disease (DED). Although the etiopathology is not completely known, the conjunctiva might be a key site of T-cell activation. The differential diagnosis might be tricky at early stages, because of the lack of dedicated clinical and laboratory tests. To meet these needs, we evaluated the suitability of ocular surface matrix metalloproteinase-9 (MMP-9) clinical test. METHODS: Consecutive GVHD patients, referred to IRCCS San Raffaele Scientific Institute, were recruited. DED patients served as controls. MMP-9 was tested through InflammaDry immunoassay kit in both groups; Ocular Surface Disease Index (OSDI) questionnaire, tear osmolarity, fluorescein Tear Break-up Time (TBUT), corneal and conjunctival staining, and Schirmer test I were also collected. Parametric and nonparametric statistical tests were used to analyze the intergroup differences; Receiver Operating Characteristics (ROC) curve analysis was carried out to perform sensitivity and specificity evaluations. RESULTS: Forty-five GVHD and 40 DED patients were included. MMP-9 expression was significantly higher in GVHD group than in DED (84.4% vs 33%, p ≤ 0.001). Corneal and conjunctival staining scores resulted worse in GVHD than in DED (0.95 ± 1.16 vs 0.40 ± 0.63, p=0.02; 0.77 ± 0.42 vs 0.40 ± 0.49, p=0.0005, respectively). No significant differences regarded the other collected parameters. GVHD group was characterized by positive correlations between MMP-9 and conjunctival staining (rho = 0.55, p=0.0002) and between MMP-9 and OSDI (rho = 0.3, p=0.01); a faint inverse correlation was found between MMP-9 and Schirmer test (rho = −0.25, p=0.04). CONCLUSION: MMP-9 has a role in physiologic cellular remodeling; when a proinflammatory stimulus occurs, MMP-9 molecules are overreleased in the extracellular matrix. The positive expression of MMP-9 in GVHD may be interpreted as the consequence of a T-cell aggression against self-antigens and may be considered a reliable biomarker to detect ocular surface inflammation in GVHD, even in early stages of the disease. Hindawi 2021-06-12 /pmc/articles/PMC8216819/ /pubmed/34234963 http://dx.doi.org/10.1155/2021/9958713 Text en Copyright © 2021 Luigi Berchicci et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Berchicci, Luigi
Aragona, Emanuela
Arrigo, Alessandro
Marchese, Alessandro
Miserocchi, Elisabetta
Bandello, Francesco
Modorati, Giulio
Conjunctival Matrix Metalloproteinase-9 Clinical Assessment in Early Ocular Graft versus Host Disease
title Conjunctival Matrix Metalloproteinase-9 Clinical Assessment in Early Ocular Graft versus Host Disease
title_full Conjunctival Matrix Metalloproteinase-9 Clinical Assessment in Early Ocular Graft versus Host Disease
title_fullStr Conjunctival Matrix Metalloproteinase-9 Clinical Assessment in Early Ocular Graft versus Host Disease
title_full_unstemmed Conjunctival Matrix Metalloproteinase-9 Clinical Assessment in Early Ocular Graft versus Host Disease
title_short Conjunctival Matrix Metalloproteinase-9 Clinical Assessment in Early Ocular Graft versus Host Disease
title_sort conjunctival matrix metalloproteinase-9 clinical assessment in early ocular graft versus host disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216819/
https://www.ncbi.nlm.nih.gov/pubmed/34234963
http://dx.doi.org/10.1155/2021/9958713
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