State of the art on the research for biomarkers allowing individual, tailor-made minimization of immunosuppression

被引:8
作者
Sawitzki, Birgit [1 ,2 ]
Reinke, Petra [2 ,3 ]
Pascher, Andreas [4 ]
Volk, Hans-Dieter [1 ,2 ]
机构
[1] Charite, Inst Med Immunol, CCM, D-10117 Berlin, Germany
[2] Charite, Berlin Brandenburg Ctr Regenerat Therapies BCRT, CVK, D-10117 Berlin, Germany
[3] Charite, Dept Nephrol & Intens Care, CVK, D-10117 Berlin, Germany
[4] Charite, Dept Surg, CVK, D-10117 Berlin, Germany
关键词
B cell; Elispot; gene marker; human leukocyte antigen antibodies; plasma cell; transplantation; RENAL-ALLOGRAFT REJECTION; TERM GRAFT FUNCTION; MESSENGER-RNA; B-CELLS; TRANSPLANTATION TOLERANCE; MAINTENANCE IMMUNOSUPPRESSION; KIDNEY-TRANSPLANTATION; LIVER-TRANSPLANTATION; OPERATIONAL TOLERANCE; NONINVASIVE DETECTION;
D O I
10.1097/MOT.0b013e32834066b0
中图分类号
R3 [基础医学]; R4 [临床医学];
学科分类号
1001 ; 1002 ; 100602 ;
摘要
Purpose of review In order to avoid toxic side effects by long-term immunosuppressive treatment, transplant research therefore focuses on new strategies to either induce tolerance or allow partial or complete immunosuppressive weaning whenever possible. This can be only safely achieved when guided by biomarkers reflecting the individual immune reactivity. Here we summarize the recent efforts to identify biomarkers and functional assays which allow an individualized minimization or complete weaning of immunosuppression in stable or 'operational' tolerant transplant patients, respectively. Recent findings Data obtained by two main collaborative networks, 'RISET' and 'Immune Tolerance Network' have provided a better characterization of operational tolerant kidney patients. In both studies an increased numbers of B cells and a B-cell-associated peripheral gene signature were discovered. Long-term observation of tolerant liver transplant patients undergoing immunosuppressive minimization highlight the importance of surveillance or protocol biopsies. Additionally, functional assays such as IFN-gamma ELISPOT or urine markers have been shown to predict long-term graft outcome. Summary With the recent findings we have gained a better understanding of operational tolerant patients and have identified biomarkers and assays which will be very helpful when guiding partial or complete immunosuppressive minimization. For the future, collaborative efforts are needed to design and perform prospective multicenter trials to validate the identified biomarkers across different laboratories and laboratory platforms.
引用
收藏
页码:691 / 696
页数:6
相关论文
共 45 条
  • [1] Minimization of Maintenance Immunosuppression Early After Renal Transplantation: An Interim Analysis
    Bemelman, Frederike J.
    de Maar, Eltjo F.
    Press, Rogier R.
    van Kan, Henrikus J.
    ten Berge, Ineke J.
    van der Heide, Jaap J. Homan
    de Fijter, Hans W.
    [J]. TRANSPLANTATION, 2009, 88 (03) : 421 - 428
  • [2] Gene Expression Profiling and Transplantation Tolerance in the Clinic
    Benitez, Carlos
    Jose Lozano, Juan
    Sanchez Fueyo, Alberto
    [J]. TRANSPLANTATION, 2009, 88 (03) : S50 - S53
  • [3] BAFF Is Increased in Renal Transplant Patients Following Treatment with Alemtuzumab
    Bloom, D.
    Chang, Z.
    Pauly, K.
    Kwun, J.
    Fechner, J.
    Hayes, C.
    Samaniego, M.
    Knechtle, S.
    [J]. AMERICAN JOURNAL OF TRANSPLANTATION, 2009, 9 (08) : 1835 - 1845
  • [4] Identification of a peripheral blood transcriptional biomarker panel associated with operational renal allograft tolerance
    Brouard, Sophie
    Mansfield, Elaine
    Braud, Christophe
    Li, Li
    Giral, Magali
    Hsieh, Szu-Chuan
    Baeten, Dominique
    Zhang, Meixia
    Ashton-Chess, Joanna
    Braudeau, Cecile
    Hsieh, Frank
    Dupont, Alexandre
    Pallier, Annaik
    Moreau, Anne
    Louis, Stephanie
    Ruiz, Catherine
    Salvatierra, Oscar
    Soulillou, Jean-Paul
    Sarwal, Minnie
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (39) : 15448 - 15453
  • [5] Ultra-localization of Foxp3+ T cells within renal Allografts shows infiltration of tubules mimicking rejection
    Brown, Kathryn
    Moxham, Victoria
    Karegli, Julieta
    Phillips, Richard
    Sacks, Steven H.
    Wong, Wilson
    [J]. AMERICAN JOURNAL OF PATHOLOGY, 2007, 171 (06) : 1915 - 1922
  • [6] Memory Alloreactive B Cells and Alloantibodies Prevent Anti-CD154-Mediated Allograft Acceptance
    Burns, Audrea M.
    Ma, Lianli
    Li, Yijin
    Yin, Dengping
    Shen, JiKun
    Xu, Jing
    Chong, Anita S.
    [J]. JOURNAL OF IMMUNOLOGY, 2009, 182 (03) : 1314 - 1324
  • [7] Monitoring of human liver and kidney allograft tolerance: a tissue/histopathology perspective
    Demetris, Anthony J.
    Lunz, John G., III
    Randhawa, Parmjeet
    Wu, Tong
    Nalesnik, Michael
    Thomson, Angus W.
    [J]. TRANSPLANT INTERNATIONAL, 2009, 22 (01) : 120 - 141
  • [8] Cutting edge: Transplant tolerance induced by anti-CD45RB requires B lymphocytes
    Deng, Shaoping
    Moore, Daniel J.
    Huang, Xiaolun
    Lian, Moh-Moh
    Mohiuddin, Muhammad
    Velededeoglu, Ergun
    Lee, Major K., IV
    Sonawane, Samsher
    Kim, James
    Wang, Jing
    Chen, Haiying
    Corfe, Steven A.
    Paige, Christopher
    Shlomchik, Mark
    Caton, Andrew
    Markmann, James F.
    [J]. JOURNAL OF IMMUNOLOGY, 2007, 178 (10) : 6028 - 6032
  • [9] Translating transplantation tolerance in the clinic: where are we, where do we go?
    Goldman, M.
    Wood, K.
    [J]. CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2009, 156 (02) : 185 - 188
  • [10] Mycophenolate Mofetil and Calcineurin-Inhibitor Reduction: Recent Progress
    Grinyo, Josep M.
    Cruzado, Josep M.
    [J]. AMERICAN JOURNAL OF TRANSPLANTATION, 2009, 9 (11) : 2447 - 2452