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HUMORAL SENSITIZATION AND REJECTION IN CAMPATH -1H TREATED KIDNEY TRANSPLANT RECIPIENTS.
M. Carreno, MD, G. Ciancio, MD, G. W. Burke, MD, J. Miller, PhD and V. Esquenazi, MD. Miami FL, USA, University of Miami, 33136, Surg.-Transp.; Miami FL, USA, VA Medical Center, 33136 and Microbiology and Immunology.
Introduction- Induction therapy with Campath 1-H (C) has shown to be safe and effective in kidney Tx. when used in combination with several different immunosuppressive protocols. We tested for the effect of antibody (ab) sensitization pre- and post-Tx. in 58 pts that received C (16 days-24 mos, mean follow-up = 10 mos).
Methods- C was given on days 0 and 4 and maintenance immunosuppression consisted of half dosages of tacro and MMF but no steroids. Biopsies were graded using the Banff scale. Sensitization was determined by Specific and High Definition beads in flow cytometry. The cytoablative effect of C was assessed serially, in peripheral blood (PBL), in ileac crest bone marrow (BM) aspirates and on cell subsets, in vitro.
Results- Six of the 58 pts experienced acute rejection during the first year. Two were C4d+. Three of the 6 had historical abs pre-Tx. Two of 3 were pre-sensitized to donor antigens (one to class I and the other to class II) while the third was against third party antigens. The other 3 rejectors were negative pre-Tx but develop anti-donor abs afterwards (2/3 to class II donor antigens). One (with anti-donor activity pre-Tx) lost the graft due to acute humoral rejection while the others were reversed with steroids, anti-lymphocyte ab and/or IVIG. Four additional patients of the 58 were pre-sensitized but did not develop kidney dysfunction. T cell subsets were decreased between 0 and 12 months post-Tx. B cells recovered by 60 days in BM, later exceeding the normal range in PBL. In addition, plasma cells (CD138+) expressing low CD52, were not affected, in vitro.
Conclusion- Pre and post-Tx monitoring of abs might aid post-Tx management, especially in pts receiving Campath-1H.