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Evaluation by histology, immunohistology and PCR of protocollized renal biopsies 1 week post-transplant in relation to subsequent rejection episodes
Authors:Kooijmans-Coutinho, M. F.   Bruijn, J. A.   Hermans, J.   Schindler, R.   Frei, U.   Schrama, E.   van Es, L. A.   Daha, M. R.   van der Woude, F. J.
Affiliation:1Department of Nephrology, Leiden University Hospital Germany 2Department of Pathology, Leiden University Hospital Germany 3Department of Statistics, Leiden University The Netherlands 4Department of Internal Medicine, Free University Berlin Germany
Abstract:Renal biopsies were performed 1 week following renal transplantationat a time without clinical evidence of rejection in 43 patients(13 females, mean age 48 years range 18–60 and 30 males,mean age 43 years range 17–59 years). Thirty-six biopsieswere available for histological or immunohistochemical analysis.Immunohistochemical analyses were performed with monoclonalantibodies against leukocytes (CD45), monocytes (WT14), complementfactor 3 (C3), T-cells (Leu4), T-cell receptor {alpha}ß and{gamma}{delta}, tumour necrosis factor {alpha}(TNF{alpha}) IL-2 receptor (IL2-R, TAC), intercellularadhesion molecule-l (ICAMI) and HLA-DR. The slides were scoredsemiquantitatively with the observers having no knowledge ofclinical or patient data. TNF{alpha} and IL-2R were also measured byquantative PCR. None of the studied parameters correlated todelayed graft function or graft loss. Histological analysisshowed that both focal interstitial infiltrate (18/35) and tubularbasement membrane disruption (11/35) were followed by a higherincidence of subsequent rejection (P = 0.03 and 0.02 respectively).Also positivity for WT14 around tubuli (P = 0.02) was associatedwith subsequent occurrence of rejection. The intensity of stainingof ICAM-I on PTC as well as TAC on proximal tubular cells wasassociated with the number of subsequent rejection episodes.The association between the IL-2 receptor and subsequent rejectionwas also found applying PCR to the tissue specimens. We conclude that the presence of focal interstitial infiltratesand tubulitis in 1-week biopsies from well-functioning graftscarries an increased risk of subsequent rejection. The observedinfiltrate outside the tubuli may consist of either monocytesor lymphocytes. Further studies, both in vitro and in vivo,applying immunohistochemical and molecular biological techniqueswill be necessary to further elucidate the role of adhesionmolecules and interleukins in early and ongoing rejection.
Keywords:renal transplantation   immunohistology   rejection   ICAM-I   IL2-R   macrophages
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