Acute Cellular Rejection Predominated by Monocytes Is a Severe Form of Rejection in Human Renal Recipients With or Without Campath-1H (Alemtuzumab) Induction Therapy

Zhang, Ping L.; Malek, Sayeed K.; Prichard, Jeffery W.; Lin, Fan; Yahya, Taher; Schwartzman, Michael S.; Latsha, R.; Norfolk, Evan; Blasick, Thomas M.; Lun, Mingyue; Brown, Robert E.; Hartle, James E.; Potdar, Santosh

doi:10.1111/j.1600-6143.2004.00712.x

Cited by 29 publications

(14 citation statements)

References 15 publications

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“…Consistent with this observation, a recent report has described the presence of CD20 positive (B-cell) lymphoid clusters in kidney allografts undergoing allograft rejection following treatment with alemtuzumab therapy (19). Similarly, another report also describes a form of monocytic rejection in renal transplant recipients following alemtuzumab therapy (20). Additional studies and long-term follow-up are needed in both our RAR and BOS patients to determine the precise histological phenotype and clinical significance of these atypical rejection patterns.…”

Section: Reams Et Alsupporting

confidence: 53%

Alemtuzumab in the Treatment of Refractory Acute Rejection and Bronchiolitis Obliterans Syndrome After Human Lung Transplantation

Reams¹,

Musselwhite²,

Zaas³

et al. 2007

American Journal of Transplantation

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Despite substantial improvements in early survival after lung transplantation, refractory acute rejection (RAR) and bronchiolitis obliterans syndrome (BOS) remain major contributors to transplant-related morbidity and mortality. We have utilized alemtuzumab, a humanized anti-CD52 antibody which results in potent lymphocyte depletion, in consecutive patients with RAR (n = 12) or BOS (n = 10). All patients failed conventional treatment with methylprednisolone and antithymocyte globulin and received strict infection prophylaxis. Alemtuzumab significantly improved histological rejection scores in RAR. Total rejection grade/biopsy was 1.98 ± 0.25 preceding alemtuzumab versus 0.33 ± 0.14 posttreatment, p-value <0.0001 (with a similar number of biopsies/patient per respective time interval). Freedom from BOS was observed in 65% of RAR patients 2 years after alemtuzumab treatment. Although there was no statistically significant change in forced expiratory volume in 1 second (FEV1) before and after alemtuzumab treatment in patients with BOS, a stabilization or improvement in BOS grade occurred in 70% of patients. Patient survival 2 years after alemtuzumab for BOS was 69%. Despite a dramatic decline in CD4 counts in alemtuzumab-treated patients, only one patient developed a lethal infection. Thus, we provide the first evidence that alemtuzumab is a potentially useful therapy in lung transplant recipients with RAR or BOS.

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Section: Reams Et Alsupporting

confidence: 53%

Alemtuzumab in the Treatment of Refractory Acute Rejection and Bronchiolitis Obliterans Syndrome After Human Lung Transplantation

Reams¹,

Musselwhite²,

Zaas³

et al. 2007

American Journal of Transplantation

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“…Similar numbers of T lymphocytes and B cells were found in rejecting renal allografts of alemtuzumab-treated patients and in allografts of patients with no induction at the time of transplantation, although the number of infiltrating monocytes was higher in the alemtuzumab group than in the no induction group. These data are consistent with a recent study by Zhang et al (10), who found similar percentages of CD3 ϩ lymphocytes and higher percentages of CD68 ϩ monocytes in the rejected grafts from patients with alemtuzumab induction therapy as compared with cases of ACR in the absence of alemtuzumab induction. Intense monocyte infiltration in the graft can be interpreted as reflecting that blood monocyte depletion after alemtuzumab is gradual and transient and lymph nodal monocytes generally are not depleted (5).…”

Section: Discussionsupporting

confidence: 83%

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

Gallon

Gagliardini

Benigni

et al. 2006

Clinical Journal of the American Society of Nephrology

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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.

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“…These cells are associated with more aggressive infiltrates (58) but typically have been dismissed in favor of lymphocyte evaluation. However, with the recent increase in depletional induction trials, the role of the monocyte as an important mediator of injury has risen in importance (38) and is increasingly being recognized as relevant in nondepletional rejection (59). Similarly, the B cell was identified recently as playing a potential role in cellular rejection.…”

Section: What More Can the Biopsy Tell Us?mentioning

confidence: 99%

Beyond Histology

Mannon¹,

Kirk²

2006

Clinical Journal of the American Society of Nephrology

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Kidney biopsy is the gold standard procedure for the assessment of allograft dysfunction. The differential diagnosis for both acute and chronic dysfunction can encompass a number of different causes, and a biopsy frequently can suggest a specific cause. However, many of these causes are difficult to distinguish on morphologic basis alone, and the information that is obtained from a biopsy is limited with regard to functional and prognostic importance. Additional methods therefore are needed to guide the diagnosis and the treatment of allograft dysfunction, and numerous methods have been studied. Potential markers include protein and gene expression profiles in the peripheral blood, the urine, and the graft itself, all compartments that are relevant to the alloimmune response. Recent comprehensive sequencing of the human genome has led to an unprecedented opportunity to develop these genetic and proteomic techniques, and ongoing evaluations of potential tests have led to an improved understanding of the complexity of immune responses. The future challenge for promising tests is validation in larger patient populations to facilitate their addition to the diagnostic armamentarium.

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Acute Cellular Rejection Predominated by Monocytes Is a Severe Form of Rejection in Human Renal Recipients With or Without Campath-1H (Alemtuzumab) Induction Therapy

Cited by 29 publications

References 15 publications

Alemtuzumab in the Treatment of Refractory Acute Rejection and Bronchiolitis Obliterans Syndrome After Human Lung Transplantation

Alemtuzumab in the Treatment of Refractory Acute Rejection and Bronchiolitis Obliterans Syndrome After Human Lung Transplantation

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

Beyond Histology

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