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Immunophenotypic Analysis of Cellular Infiltrate of Renal Allograft Biopsies in Patients with Acute Rejection after Induction with Alemtuzumab (Campath-1H)

Lorenzo Gallon^*,, Elena Gagliardini, Ariela Benigni, Dixon Kaufman, Ahmed Waheed^*, Marina Noris, and Giuseppe Remuzzi

Divisions of ^* Nephrology and Solid Organ Transplantation, Northwestern University, Chicago, Illinois; and Department of Medicine and Transplantation, Ospedali Riuniti-Mario Negri Institute for Pharmacologic Research, Bergamo, Italy

Address correspondence to: Dr. Lorenzo Gallon, Northwestern University, 675 N. St. Clair, Galter Pavilion 17-200, Chicago, IL 60611. Phone: 312-695-4457; Fax: 312-695-9194; E-mail: l-gallon{at}northwestern.edu

Alemtuzumab is a humanized anti-CD52 mAb that has emerged as a safe and effective lymphocyte-depleting agent for induction therapy in renal transplantation. Recent reports have suggested that acute cellular rejection (ACR) of renal allografts in patients who receive alemtuzumab induction may be mediated by an atypical population of monocytes and not through "classical" T cell-dependent pathways of allorecognition. However, more recently, T cells with memory phenotype have been described in renal biopsies that were taken from alemtuzumab-treated patients who were experiencing ACR. This study investigated the cellular basis of ACR after alemtuzumab induction as compared with ACR that was associated with nondepleting therapy. Twelve biopsies from patients who were treated with a single dose of alemtuzumab at the time of transplantation and subsequently developed ACR were stained for the following cell markers: CD3 (T cells), CD68 (monocytes), CD20 (B cells), and CD45RO and CD45RA (memory and naïve T cells). ACR biopsies from six patients who received no induction therapy were used as controls. In alemtuzumab-treated patients, ACR occurred despite profound lymphopenia. A consistent number of CD3⁺ T cells was found in all ACR biopsies, and the majority of infiltrating CD3⁺ T cells displayed a memory phenotype (CD45RO⁺, CD45RA^–). The number of infiltrating CD3⁺ T cells and B cells (CD20⁺) was similar in the two groups of patients, whereas a higher number of monocytes (CD68⁺) were found in the alemtuzumab than in the control group. Despite profound peripheral T cell depletion by alemtuzumab, ACR occurs and is associated with T and B cell and monocyte infiltration of the kidney. Specifically, T cells express on their surface the memory phenotype, suggesting that memory T cells may have eluded the depleting agent.

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