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M Hillarby, PA Kallinikos, JM Prince, JA Dixon, AB Tullo; LFA-1 is Upregulated by Peripheral Lymphocytes During Human Corneal Transplant Rejection . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2218.
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Purpose: Corneal transplantation has a high success rate. However, a small proportion of corneal graft recipients do experience episodes of rejection. Fas levels on peripheral blood lymphocytes are significantly reduced during episodes of rejection. This reduction in Fas expression may be important in rejection but other factors are also involved (1). The aim of this study was to identify other genes that play a role in corneal graft rejection. Methods: RNA was extracted from blood samples taken from two corneal graft patients, one at the time of rejection and one who had not rejected and was matched for age, sex, time after graft and reason for graft. Following RT-PCR using the Clontech BD's SMART cDNA synthesis method, radioactive micro array analysis was performed using individual Atlas Cell Interaction arrays for each patient and analysed using Atlas Image 1.5 software. Results: A number of genes were identified as been up or down regulated during transplant rejection. One gene, LFA-1 (Lymphocyte Function associated antigen 1), which was up regulated, was studied further by a semi quantitative RT-PCR on 13 rejecting, 22 non-rejecting patients and 9 normal controls. The housekeeping gene ß-actin was used to standardise the quantitation and the results were expressed as the ratio LFA-1:ßactin. LFA-1 was increased significantly in the rejecting patient group (mean ratio = 0.689) when compared to normal controls (mean ratio = 0.192, p<0.0001) and non-rejecting patients (mean ration = 0.226, p<0.0001). Conclusion: LFA-1 (A member of the integrin family which binds ICAM-1) is significantly increased in peripheral blood lymphocytes during episodes of corneal graft rejection and may prove to be a useful prognostic marker or a target for treatment and/or prevention of graft rejection. 1. Dixon JA, Reynolds I, Tullo AB, Zeggini E, Hillarby MC. (2001). Fas mRNA expression is reduced in human corneal graft rejection. Transplantation. 72:702-704
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