Differential chemokine expression in chronic GVHD of the conjunctiva.
In chronic GVHD after BMT, the conjunctiva represents a target organ. GVHD can lead to severe inflammation and dry-eye syndrome (sicca syndrome). The molecular mechanisms are largely unknown. We examined the expression of chemokines in the conjunctiva in cases of chronic GVHD. In this study, we included 10 patients with chronic GVHD and 10 healthy controls. Clinical data were collected and tear film analysis and conjunctival cytology were carried out. Conjunctival biopsies were taken from all participants. Gene expression profiles of chemokines and their corresponding receptors were evaluated by means of quantitative real-time PCR. Chemokine protein expression was analysed by immunohistochemical analyses. Expressions of the Th1-associated chemokines, chemokine (C-X-C motif) ligand (CXCL) 9 (Mig), CXCL10 (IP-10), and their receptor chemokine (C-X-C motif) receptor 3 (CXCR3) were significantly increased in GVHD patients. Immunohistochemical analysis confirmed marked expression of the inflammatory CXCR3 ligands. A total of six patients had a moderate or severe sicca syndrome. Impression cytology revealed a mild keratinisation, moderate keratinisation or severe squamous metaplasia in three patients, respectively. Chronic GVHD of the conjunctiva is characterised by the expression of Th1-associated chemokines. Taken together, our results confirm that the conjunctiva is a target organ in this T cell-mediated process and add to molecular understanding of conjunctival GVHD.
Department of Ophthalmology, University of Duisburg-Essen, Essen, Germany.
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Westekemper
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Meller
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Citak
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Schulte
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Steuhl
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Homey
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Meller
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D016022:Case-Control Studies; D018925:Chemokines / Q000032:analysis* / Q000235:genetics; D002908:Chronic Disease; D003229:Conjunctival Diseases / Q000235:genetics / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D006086:Graft vs Host Disease / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019707:Receptors, Chemokine / Q000032:analysis / Q000235:genetics; D018417:Th1 Cells / Q000378:metabolism; D055815:Young Adult
D018925:Chemokines; D019707:Receptors, Chemokine