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lüll Herpes simplex virus keratitis: histopathologic inflammation and corneal allograft rejection Shtein RM; Garcia DD; Musch DC; Elner VMOphthalmology 2009[Jul]; 116 (7): 1301-5OBJECTIVE: To identify whether histopathologic and immunoassay biomarkers of inflammation are predictive for allograft rejection after penetrating keratoplasty (PKP) for herpes simplex virus (HSV) keratitis. DESIGN: Retrospective, interventional case series with prospective component of pathologic evaluation of frozen tissue. PARTICIPANTS: Sixty-two consecutive patients with HSV keratitis who underwent PKP. METHODS: A chart review and histopathologic examination of the excised host corneal button was performed to identify associations between clinical data and histopathologic presence of inflammation. Enzyme-linked immunosorbent assay for interleukin (IL)-8 and monocyte chemotactic protein-1 (MCP-1) chemokines and immunohistochemical staining for human leukocyte antigen (HLA)-DR and intercellular adhesion molecule-1 (ICAM-1) antigens was also performed in inflamed and noninflamed specimens. MAIN OUTCOME MEASURES: To determine whether the presence of subclinical inflammation at the time of PKP predicts allograft rejection. RESULTS: Although 81% of patients had clinically quiescent disease, histopathology revealed that 74% had active corneal inflammation, a finding that was associated with the presence of clinical neovascularization (P = 0.01). Allograft rejections were experienced by 34% of the patients in this cohort. The histopathologic presence of inflammation was a risk factor for allograft rejection (P = 0.02). Corneal specimens demonstrating inflammation had significantly increased IL-8 (P = 0.0005) and MCP-1 (P = 0.003) levels, and greater immunoreactivity for HLA-DR and ICAM-1 when compared with specimens without inflammation. Treatment with IL-10 ex vivo significantly inhibited IL-8 (P = 0.006), and MCP-1 (P = 0.01) chemokines, and qualitatively substantially reduced HLA-DR, but not ICAM-1, expression. CONCLUSIONS: Histopathologic inflammation is a risk factor for corneal allograft rejection.|*Keratoplasty, Penetrating[MESH]|Adolescent[MESH]|Adult[MESH]|Aged[MESH]|Aged, 80 and over[MESH]|Biomarkers/metabolism[MESH]|Chemokine CCL2/metabolism[MESH]|Chemokines/metabolism[MESH]|Child[MESH]|Child, Preschool[MESH]|Cornea/metabolism/*pathology[MESH]|Enzyme-Linked Immunosorbent Assay[MESH]|Female[MESH]|Graft Rejection/*diagnosis/etiology/metabolism[MESH]|HLA-DR Antigens/metabolism[MESH]|Humans[MESH]|Inflammation/*diagnosis/metabolism[MESH]|Intercellular Adhesion Molecule-1/metabolism[MESH]|Interleukin-8/metabolism[MESH]|Keratitis, Herpetic/metabolism/*surgery[MESH]|Male[MESH]|Middle Aged[MESH]|Retrospective Studies[MESH]|Risk Factors[MESH]|Transplantation, Homologous[MESH]|Young Adult[MESH] |