Herpes simplex virus keratitis: histopathologic inflammation and corneal allograft rejection.
OBJECTIVE
To identify whether histopathologic and immunoassay biomarkers of inflammation are predictive for allograft rejection after penetrating keratoplasty (PKP) for herpes simplex virus (HSV) keratitis.


METHODS
Retrospective, interventional case series with prospective component of pathologic evaluation of frozen tissue.


METHODS
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.


METHODS
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.
Shtein
Roni M
RM
Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, USA.
Garcia
Denise D
DD
Musch
David C
DC
Elner
Victor M
VM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003315:Cornea / Q000378:metabolism / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000175:diagnosis* / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D016849:Keratitis, Herpetic / Q000378:metabolism / Q000601:surgery*; D015948:Keratoplasty, Penetrating; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D014184:Transplantation, Homologous; D055815:Young Adult
D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D018925:Chemokines; D006684:HLA-DR Antigens; D016209:Interleukin-8; D018799:Intercellular Adhesion Molecule-1