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Correlation Between Human Leukocyte Antigen Antibody Production and Serum Creatinine in Patients Receiving Sirolimus Monotherapy after Campath-1H Induction

Cai, Junchao1; Terasaki, Paul I.1; Bloom, Debra D.2; Torrealba, Jose R.3; Friedl, Andreas3; Sollinger, Hans W.2; Knechtle, Stuart J.2,4

doi: 10.1097/01.TP.0000134398.86243.81
Clinical Transplantation

Background. In this study, we determined whether Campath-1H induction followed by sirolimus monotherapy inhibited alloantibody production in renal transplantation. Second, we evaluated the correlation between human leukocyte antigen (HLA) antibody production and serum creatinine levels.

Methods. Sera were taken 1 to 24 months after transplantation from 24 patients treated with Campath-1H and sirolimus and tested for serum creatinine and HLA-specific antibody by using flow cytometry and enzyme-linked immunosorbent assay.

Results. Ten (42%) of the 24 patients treated with Campath-1H and sirolimus produced HLA antibodies. Six of these 10 developed both donor-specific antibodies (DSAs) and non–donor-specific antibodies (NDSAs), whereas only NDSAs were detected in the other four patients. In patients with biopsy-diagnosed humoral rejection (C4d+), serum levels of both DSA and NDSA significantly correlated with patient serum creatinine levels. Rejection treatment successfully reduced both DSAs and NDSAs and reversed humoral rejection.

Conclusions. The numeric relationship between serum creatinine and DSA levels suggests a causal relationship between alloantibody and transplant rejection.

1 Terasaki Foundation Laboratory, Los Angeles, California.

2 Department of Surgery, University of Wisconsin Medical School, Madison, Wisconsin.

3 Department of Pathology and Laboratory Medicine, University of Wisconsin Medical School, Madison, Wisconsin.

This work was supported by National Institutes of Health grant R01 AI50938 to S.J.K. and by the Terasaki Foundation.

4 Address correspondence to: Stuart J. Knechtle, M.D., Department of Surgery, University of Wisconsin Hospital, 600 Highland Avenue, Madison, WI 53792–7375. E-mail:

Received 20 November 2003. Revision requested 14 December 2003. Accepted 30 April 2004.

© 2004 Lippincott Williams & Wilkins, Inc.