N Babel

Publications (11)46.15 Total impact

• Article: Cytomegalovirus-specific regulatory and effector T cells share TCR clonality--possible relation to repetitive CMV infections.

  S Schwele, A M Fischer, G Brestrich, M W Wlodarski, L Wagner, M Schmueck, A Roemhild, S Thomas, M H Hammer, N Babel, A Kurtz, J P Maciejewski, P Reinke, H-D Volk
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  ABSTRACT: Cytomegalovirus (CMV) infections have a major impact on morbidity and mortality of transplant patients. Among the complex antiviral T-cell response, CMV-IE-1 antigen-specific CD8+ cells are crucial for preventing CMV disease but do not protect from recurring/lasting CMV reactivation. Recently, we confirmed that adoptive transfer of autologous IE-1/pp65-specific T-cell lines was able to combat severe CMV disease; however, the control of CMV infection was only temporary. We hypothesized that CMV-induced regulatory T cells (iTreg) might be related to recurring/lasting CMV infection. In fact, kidney transplant patients with recurring CMV infections expressed enhanced suppression on CMV response. Analysis of in vitro expanded CD4+ epitope-specific cells revealed that CMV-specific CD4+CD25(high) Treg cells functionally suppress CD25(low) effector T cells (Teff) upon epitope-specific reactivation. Their phenotype is similar to iTreg - CD39(high) /Helios-/IL-2(low) /IFNγ(high) /IL-10±/TGFß-LAP±/FOXP3+ and methylated foxp3 locus. Remarkably, in vitro expanded CD4+CD25(high) iTreg share the same dominant TCR-Vβ-CDR3 clones with functionally distinct CD4+CD25(low) Teff. Moreover, the same clones were present in freshly isolated CD4+CD25(high) and CD4+CD25(low) T cells suggesting their in vivo generation. These findings directly demonstrate that Teff and iTreg can differentiate from one "mother" clone with specificity to the same viral epitope and indicate that peripheral iTreg generation is related to frequent antigen appearance.
  American Journal of Transplantation 11/2011; 12(3):669-81. · 6.39 Impact Factor
• Article: BK virus-specific immunity kinetics: a predictor of recovery from polyomavirus BK-associated nephropathy.

  T Schachtner, K Müller, M Stein, C Diezemann, A Sefrin, N Babel, P Reinke
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  ABSTRACT: Impaired BKV-specific immunity is associated with development of BKV-associated nephropathy. Suitable immunological parameters to identify patients at risk, however, are still debated. We monitored 18 kidney-transplant recipients through the course of self-limited BKV-reactivation (n = 11) and BKV-associated nephropathy (n = 7). BKV-specific cellular immunity directed to nonstructural small and Large T-antigen, and structural VP1-3 was analyzed in an interferon-γ Elispot assay. BKV-specific IgM and IgG were measured using an enzyme-linked immunosorbent assay simultaneously. BKV-specific cellular immunity directed to five BKV-proteins increased significantly from diagnosis to resolution of BKV-reactivation (p < 0.001). Patients with self-limited BKV-reactivation developed BKV-specific T cells without therapeutic interventions, and cleared BKV-reactivation within a median period of 1 month. Patients with BKV-associated nephropathy, however, showed BKV-specific T cells after a median period of 5 months after therapeutic interventions only, and cleared BKV-reactivation after a median period of 8 months. Anti-structural T cells were detected earlier than anti-nonstructural T cells, which coincided with BKV-clearance. Patients with BKV-associated nephropathy showed the highest frequencies of BKV-specific T cells at recovery, the highest increase in BKV-specific IgG and persistence of increased IgM levels (p < 0.05). Our results suggest prognostic values of BKV-specific immune monitoring to identify those patients at risk of BKV-associated nephropathy and to aid in the management of therapeutic interventions.
  American Journal of Transplantation 08/2011; 11(11):2443-52. · 6.39 Impact Factor
• Article: Treatment of PTLD with rituximab and CHOP reduces the risk of renal graft impairment after reduction of immunosuppression.

  R Trappe, C Hinrichs, U Appel, N Babel, P Reinke, H-H Neumayer, K Budde, M Dreyling, U Dührsen, V Kliem, S Schüttrumpf, I A Hauser, H-G Mergenthaler, P Schlattmann, I Anagnostopoulos, B Doerken, H Riess
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  ABSTRACT: We addressed the effect of post-transplant lymphoproliferative disorder (PTLD) treatment with rituximab monotherapy or CHOP-based chemotherapy (+/- rituximab) after upfront immunosuppression reduction (IR) on renal graft function in a longitudinal analysis of 58 renal transplant recipients with PTLD and 610 renal transplant controls. Changes in the estimated glomerular filtration rate over time were calculated from a total of 6933 creatinine measurements over a period of >1 year using a linear mixed model with random and fixed effects. Renal graft function significantly improved with treatment of PTLD, especially in the chemotherapy subgroup. Patients treated with IR+chemotherapy +/- rituximab had a noninferior graft function compared with untreated controls suggesting that the negative impact of IR on the renal graft function can be fully compensated by the immunosuppressive effect of CHOP. The immunosuppressive effect of single agent rituximab may partially compensate the negative impact of IR on the graft function. Thus, it is possible to reduce immunosuppression when using chemotherapy to treat PTLD.
  American Journal of Transplantation 08/2009; 9(10):2331-7. · 6.39 Impact Factor
• Article: Development of Kaposi's sarcoma under sirolimus-based immunosuppression and successful treatment with imiquimod.

  N Babel, N Eibl, C Ulrich, G Bold, A Sefrin, M H Hammer, C Rosenberger, P Reinke
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  ABSTRACT: Kaposi's sarcoma (KS) is a vascular neoplasm typically observed in the immunocompromised patient populations, such as acquired immunodeficiency syndrome or transplant patients. KS can appear simultaneously at multiple sites as red to purple, maculo-papular or nodular cutaneous lesions sometimes showing a visceral extension. Sirolimus, an immunosuppressive agent with potent antitumor activity, has been effective in combating post-transplant KS. However, an aggressive regimen of immunosuppression for therapy of severe acute rejection episodes may abolish the antitumor effects of sirolimus. The following is a description of KS development under immunosuppressive therapy with sirolimus, and the successful treatment of KS lesions utilizing the topical application of imiquimod 5% cream, an immune response modifier.
  Transplant Infectious Disease 02/2008; 10(1):59-62. · 2.22 Impact Factor
• Source

  Available from: Mir-Farzin Mashreghi

  Article: Early post-transplant urinary IP-10 expression after kidney transplantation is predictive of short- and long-term graft function.

  M Matz, J Beyer, D Wunsch, M-F Mashreghi, M Seiler, J Pratschke, N Babel, H-D Volk, P Reinke, K Kotsch
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  ABSTRACT: The early identification of renal transplant recipients at enhanced risk of developing acute and subclinical rejection would allow individualized adjustment of immunosuppression before functional graft injury occurs and would exclude these patients from drug-weaning studies. Protein and reverse transcriptase-polymerase chain reaction-based analyses of candidate markers in urine open the opportunity to closely monitor kidney-transplanted patients non-invasively. The chemokine interferon-inducible protein 10 (IP-10; CXCL10) might be an interesting candidate to uncover ongoing immune processes within the graft. Urine samples from kidney-transplanted recipients were retrospectively analyzed for IP-10 mRNA and protein expression. IP-10 levels were correlated with the incidence of acute rejection episodes proven by histology and long-term graft function assessed by the glomerular filtration rate 6 months post transplantation. IP-10 expression in urine identified patients with ongoing acute rejection episodes several days before a biopsy was indicated by rising serum creatinine levels. Most importantly, elevated levels of urinary IP-10 protein within the first four postoperative weeks were predictive of graft function at 6 months even in the absence of acute rejection. These data reveal a correlation between elevated IP-10 expression in urine at early time points post-transplantation and intragraft immune activation that leads to acute rejection and compromised long-term graft function.
  Kidney International 06/2006; 69(9):1683-90. · 6.61 Impact Factor
• Article: HLA type-independent method to monitor polyoma BK virus-specific CD4 and CD8 T-cell immunity.

  M H Hammer, G Brestrich, H Andree, E Engelmann, C Rosenberger, H Tillmann, S Zwinger, N Babel, P Nickel, H-D Volk, P Reinke
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  ABSTRACT: (Re)activation of quiescent viral diseases is a major problem in immunosuppressed transplant patients. Polyoma BK virus-associated nephropathy (PVAN) caused by active polyoma BK virus (BKV) infection became a main reason for graft loss in kidney transplantation. After diagnosis, most transplant centers react by reducing immunosuppression (IS) to allow the immune system to control the infection. However, the impact of reduced IS on BKV immunity is not well researched. Here we present an HLA type-independent method to monitor BKV-specific T-cell immunity. Applying our method, viral protein 1-specific CD4+ and CD8+ T-cell responses were detected in patients with serum BKV-DNA levels >250 000 copies/mL. In addition, specific T-cell responses were also found in allograft-infiltrating cells. The method can be used to assess the impact of decreased immunosuppression on BKV immunity and to clarify the role of specific T cells in the pathogenesis of PVAN. We strongly recommend its implementation in future clinical studies.
  American Journal of Transplantation 03/2006; 6(3):625-31. · 6.39 Impact Factor
• Article: Monoclonal gammopathy of undetermined significance (MGUS) is associated with an increased frequency of Epstein-Barr Virus (EBV) latently infected B lymphocytes in long-term renal transplant patients.

  N Babel, F Schwarzmann, A Pruss, H-D Volk, P Reinke
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  ABSTRACT: Monoclonal gammopathy of undetermined significance (MGUS) is a common phenomenon in kidney transplant patients that might be a prestage of posttransplant lymphoproliferative disease (PTLD). Because the role of Epstein-Barr virus (EBV) for PTLD development is well established, we wondered about the association between EBV and MGUS. Thus, B-cells from kidney transplant patients (25 with and 100 without MGUS) and from 100 healthy controls were analyzed for EBV latent (EBER1) and lytic (EA, VCA) gene expression by RT-nested PCR. The EBV load was measured by real-time PCR. A significantly higher EBV load and expression of the nonimmunogenic latency associated EBER 1 gene was observed in patients with MGUS compared to both control groups (P < .001). In addition, a rare detection of the highly immunogenic lytic transcripts demonstrated a linkage between latency-associated EBV infection and MGUS in transplant patients. This pattern was similar to EBV-associated B-cell lymphomas in nonimmunosuppressed patients. It contrasted with PTLD patients who express higher EBV loads and both lytic and latent EBV transcripts. These data suggest that transplant patients with MGUS demonstrate a more sufficient control of EBV-infected B-cells. Nevertheless, EBV monitoring should be performed in patients with EBV-associated MGUS for early detection of later PTLD.
  Transplantation Proceedings 12/2004; 36(9):2679-82. · 1.00 Impact Factor
• Article: [Adoptive transfer of Epstein-Barr virus-specific T-lymphocytes in chronic active Epstein-Barr infection].

  N Babel, M H Hammer, P Reinke
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  ABSTRACT: A 27-year-old man was admitted because of intermittent fever, fatigue, lymphadenopathy and splenomegaly for 20 years. Chronic administration of 6 - 8 g aspirin per day (self-prescribed) resulted in limited control of symptoms and in the development of analgesic nephropathy. The patient had prominent splenomegaly and lymphadenopathy without histological signs of malignancy. Monocytosis and T-lymphopenia were also present. Infectious disease testing revealed IgG+/IgM- EBV serology and EA-EBV-mRNA nested PCR clearly demonstrated the presence of lytic EBV-proteins in PBMCs. As chronic active Epstein-Barr virus infection (CAEBV) was highly probable, treatment with aciclovir, gancilovir and steroids was started. Because treatment failed adoptive T-cell transfer with autologous EBV-specific T-cells was performed. After three consecutive infusions the patient responded with a complete remission of fever, fatigue, lymphadenopathy and splenomegaly without adverse effects. Retrospective real-time PCR analysis showed a decrease in viral load from 62847 copies/ microg DNA to 45 - 250 copies after treatment. The patient remains in stable remission without signs of CAEBV (> 4 years). Adoptive transfer of autologous, EBV-specific T-lymphocytes is a promising treatment in CAEBV.
  DMW - Deutsche Medizinische Wochenschrift 03/2003; 128(11):548-50. · 0.53 Impact Factor
• Article: Donor or recipient origin of posttransplantation lymphoproliferative disorders: the traces of the Epstein-Barr virus.

  H D Volk, N Babel, P Reinke
  Transplantation 09/2001; 72(3):361-2. · 4.00 Impact Factor
• Article: Association between Epstein-Barr virus infection and late acute transplant rejection in long-term transplant patients.

  N Babel, F Schwarzmann, N Prang, M Jaeger, H Wolf, F Kern, H D Volk, P Reinke
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  ABSTRACT: Recently we reported about a possible involvement of extrarenal systemic cytomegalovirus (CMV) infection in graft deteriorating immune processes. We now examined whether Epstein-Barr virus (EBV) may also be associated with late renal graft injury. We analyzed the expression of early antigen-, viral capsid antigen-, and a latency-associated EBV-RNA-transcript, which is not translated into protein in peripheral blood mononuclear cells of kidney transplant patients with histologically proven late acute rejection and no signs of CMV or any other infection (A), patients with stable graft function (B), and healthy probands (C). A total of 40% in group A vs. 5 and 0% in groups B and C, respectively, expressed early antigen-mRNA (P<0.05) suggesting an activation of lytic EBV infection. Response to steroid bolus therapy in group A was comparably poor with that observed in CMV-related graft injury. Our data suggest that extrarenal lytic EBV infection may also be involved in the pathogenesis of late graft injury. A controlled ganciclovir trial may prove the significance of our observation.
  Transplantation 08/2001; 72(4):736-9. · 4.00 Impact Factor
• Article: Induction of pre-transplant Epstein-Barr virus (EBV) infection by donor blood transfusion in EBV-seronegative recipients may reduce risk of post-transplant lymphoproliferative disease in adolescent renal transplant patients: report of two cases.

  N Babel, L Gabdrakhmanova, M Hammer, C Rosenberger, M Oppert, H-D Volk, P Reinke
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  ABSTRACT: Post-transplant lymphoproliferative disease (PTLD) is a life-threatening complication following organ transplantation. The greatest risk is seen in Epstein-Barr virus (EBV)-seronegative patients receiving allografts from EBV-seropositive donors. We demonstrate a new approach of pre-transplant prophylaxis of EBV-related PTLD, suggesting that, prior to living-related renal transplantation, blood transfusion from an EBV-seropositive donor to an EBV-seronegative recipient could induce primary EBV infection in the recipient, developing EBV immunity and decreasing risk of PTLD. Recipients underwent weekly donor-specific blood transfusion (3 x 100 mL) before transplantation. EBV-mRNA expression, viral load, serological tests, and clinical signs of EBV infection were assessed following blood transfusion. We explored a new approach in 2 young EBV-seronegative renal allograft recipients. Both patients developed primary EBV infection following blood transfusion before transplantation and showed symptom-free seroconversion post-transplantation without persistent EBV activation. There were no signs of PTLD during 5-year follow-up. A new effective and inexpensive approach is suggested for development of EBV immunity and probably for prophylaxis of EBV-associated PTLD.
  Transplant Infectious Disease 7(3-4):133-6. · 2.22 Impact Factor