CD4 lymphocytopenia in long-term renal transplant recipients

Ducloux, Didier; Carron, Pierre-Louis; Racadot, E; Rebibou, Jean-Michel; Bresson-Vautrin, Catherine; Saint‐Hillier, Y; Chalopin, Jean-Marc

doi:10.1016/s0041-1345(98)00843-4

Cited by 38 publications

(33 citation statements)

References 8 publications

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“…The influence of CD4 T cell lymphopenia on survival persisted even after return to dialysis and immunosuppressive withdrawal. We previously reported that RTRs with persistent CD4 T cell lymphopenia have an increased risk for opportunistic infections, 6 cancer, 7,8 and atherosclerotic disease. 9 Our results here add to the clinical impact of immune reconstitution after ATG administration in RTRs and underlines the need for both pretransplantation recognition of patients who are at risk for impaired immune reconstitution and posttransplantation monitoring of CD4 T cell after ATG administration to guide preventive measures.…”

Section: Discussionmentioning

confidence: 99%

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Prolonged CD4 T Cell Lymphopenia Increases Morbidity and Mortality after Renal Transplantation

Ducloux

Courivaud

Bamoulid

et al. 2010

Journal of the American Society of Nephrology

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Prolonged CD4 T cell lymphopenia after administration of polyclonal anti-thymocyte globulins increases the rate of posttransplantation morbidity, but whether impaired immune reconstitution affects survival is unknown. We studied the effect of CD4 T cell lymphopenia on survival in 302 consecutive prevalent renal transplant recipients and the role of thymic function in CD4 T cell reconstitution and posttransplantation outcomes in 100 consecutive incident renal transplant recipients. We followed the prevalent cohort for a mean duration of 92 months. Of these 302 patients, 81 (27%) had persistent CD4 T cell counts Ͻ300/mm 3 and 36 (12%) died during follow-up. We observed a higher death rate in patients with CD4 T cell lymphopenia persisting for Ͼ1 year (24.1 versus 7.6%; P Ͻ 0.001). Furthermore, in Cox regression analysis, CD4 T cell lymphopenia associated with a nearly five-fold risk for death (adjusted hazard ratio [HR] 4.63; 95% confidence interval [CI] 1.91 to 10.65; P ϭ 0.001). In the incident cohort, we estimated thymic function by T cell receptor excision circles (TRECs) per 150,000 CD3 ϩ cells, which predicted efficient CD4 T cell reconstitution. Higher pretransplantation TREC values associated with lower risks for cancer (adjusted HR 0.39; 95% CI 0.15 to 0.97; P ϭ 0.046) and infection (HR 0.29; 95% CI 0.11 to 0.78; P ϭ 0.013). In summary, prolonged polyclonal anti-thymocyte globulin-induced CD4 T cell lymphopenia is an independent risk factor for death. Determination of pretransplantation thymic function may identify patients at higher risk for CD4 T cell lymphopenia and posttransplantation morbidity, including cancer and infections. Broad T cell depletion by polyclonal anti-thymocyte globulins (ATG) has been used for many years as a part of immunosuppressive treatment in transplantation. These polyclonal antibodies are a complex mixture of antibodies with multiple specificities directed to both T and non-T cells. 1,2 These antibodies produce profound T cell depletion via complement-dependent lysis and Fas/Fas ligand-mediated apoptosis. 3,4 Although T cell regeneration generally occurs in the months after ATG administration, Muller et al. 5 reported that ATG may induce persistent changes in T cell subsets characterized by a low CD4 T cell count and a CD8 T cell expansion.

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Section: Discussionmentioning

confidence: 99%

“…Indeed, renal transplant recipients (RTRs) with persistent CD4 T cell lymphopenia exhibit a higher rate of late opportunistic infections 6 and an increased incidence of cancers. 7,8 More recently, we reported an increased rate of atherosclerotic events (AEs) in patients with impaired CD4 T cell reconstitution.…”

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confidence: 99%

Prolonged CD4 T Cell Lymphopenia Increases Morbidity and Mortality after Renal Transplantation

Ducloux

Courivaud

Bamoulid

et al. 2010

Journal of the American Society of Nephrology

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“…63 In addition, a lower average CD4 T-cell count was associated with increased risk of NMSC in one prospective study. 64 Although an association with various measures of the intensity of immunosuppression has not been a consistent finding, there is universal agreement that the incidence of NMSC increases with increasing time after transplantation. 9,56,59,65 Independent of their immunosuppressive effects, there is laboratory evidence that azathioprine and cyclosporine have direct biological effects capable of enhancing UVR-related carcinogenesis.…”

Section: Nonmelanoma Skin Cancermentioning

confidence: 99%

Cancer incidence and risk factors after solid organ transplantation

Vajdic

Leeuwen

2009

Intl Journal of Cancer

374

253

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Iatrogenic immunosuppression is a unique setting for investigating immune-related mechanisms of carcinogenesis. Solid organ transplant recipients have a 3-fold excess risk of cancer relative to the age-and sex-matched general population. Population-based studies utilizing cancer registry records indicate that a wide range of cancers, mostly those with a viral etiology, occur at excess rates. To date, cancer risk has predominantly been examined in adult kidney transplant recipients in Western countries. It is yet to be established whether a similar incidence profile exists in the longterm for other solid organ, pediatric and non-Western transplant recipients. The cancer incidence profile before and after kidney transplantation strongly suggests a relatively minor contribution by both preexisting cancer risk factors and the conditions underlying end-stage kidney disease, and points to a causal role for immunosuppression. Within-cohort risk factor analyses have largely been performed on cohorts with voluntary cancer notification, and very few have incorporated biomarkers of the level of immunosuppression, the current receipt of immunosuppressive agents, or genetic risk factors. Because of their markedly high risk of certain cancers, findings from comprehensive studies in transplant recipients have the potential to raise new avenues for investigation into causal mechanisms and preventive measures against immunerelated and infectious causes of cancer. ' UICCKey words: cancer; transplantation; immunosuppression; incidence; risk; infection; kidney A wide-ranging excess risk of cancer after solid organ transplantation has been increasingly recognized over recent decades as advances in medicine have extended the life of transplant recipients. Malignancy is now a leading cause of patient death with graft function, 1-3 an outcome that can predominantly be attributed to the iatrogenic immunosuppression required to avoid rejection of the transplanted organ. Solid organ transplantation provides a unique setting for the identification of cancers under immunological control, and for examination of the risk factors for their development. Knowledge of the range of increased cancers and the magnitude of the increased risks is important in developing appropriate prevention and early detection programs for patients undergoing long-term immunosuppression. In addition, comparison of cancer incidence and risk factors between populations with different forms of immune system impairment offers insight into carcinogenic mechanisms that has ramifications for cancer control not only in these populations but also in the general community.This review focuses on the cancer incidence profile in solid organ transplant recipients, and the established and emerging risk factors for 5 cancers that occur at increased rates. Cancer incidence after solid organ transplantationShortly after the widespread introduction of solid organ transplantation, it became apparent that immune suppression was associated with a strikingly increased risk of a few canc...

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“…The prevailing theory for skin cancer development in SOTRs is that due to diminished immune surveillance, an enhancement of UVinduced DNA damage allows atypical cells to survive and proliferate 6,7 . This theory is supported by Ducloux et al 8 , who discovered that renal transplant recipients with skin cancers had significantly lower mean CD4+ T-cell counts than those without skin cancer. Moreover, SOTRs are seven-times more likely to develop non-melanoma skin cancer when compared to AIDS patients 9 .…”

Section: Introductionmentioning

confidence: 78%

Clinical Findings, Treatments and Outcomes of Transplant Recipients with Metastatic Skin Cancer

2017

ARC Journal of Dermatology

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CD4 lymphocytopenia in long-term renal transplant recipients

Cited by 38 publications

References 8 publications

Prolonged CD4 T Cell Lymphopenia Increases Morbidity and Mortality after Renal Transplantation

Prolonged CD4 T Cell Lymphopenia Increases Morbidity and Mortality after Renal Transplantation

Cancer incidence and risk factors after solid organ transplantation

Clinical Findings, Treatments and Outcomes of Transplant Recipients with Metastatic Skin Cancer

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