Immune reactivity of renal transplant recipients receiving interleukin-2 receptor antagonists during the early posttransplant period

被引:0
作者
Zivcic-Cosic, Stela [1 ]
Lisjak, Jasna [2 ]
Racki, Sanjin [1 ]
Trobonjaca, Zlatko [2 ]
机构
[1] Univ Rijeka, Sch Med, Univ Hosp Rijeka, Dept Nephrol & Dialysis,Dept Internal Med, Rijeka 51000, Croatia
[2] Univ Rijeka, Sch Med, Dept Physiol & Immunol, Rijeka 51000, Croatia
关键词
IL-2R antagonists; Flow cytometry; Immunosuppression; Lymphocyte cell cycle; Kidney transplantation; SOLID-ORGAN TRANSPLANTATION; MYCOPHENOLATE-MOFETIL; MONOCLONAL-ANTIBODIES; KIDNEY-TRANSPLANTATION; ALLOGRAFT REJECTION; CLINICAL-RELEVANCE; LYMPHOCYTES-T; DACLIZUMAB; ACTIVATION; METAANALYSIS;
D O I
10.1007/s11255-013-0413-3
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
There is a need for methods that would enable monitoring of the effects of immunosuppression on the recipient's immune system to avoid rejection, immunodeficiency-related complications and non-immune toxicities of the drugs used in therapy. This prospective trial included thirty patients who underwent renal transplantation in our center. All patients received an interleukin-2 receptor (IL-2R) antagonist in combination with mycophenolate, corticosteroid and calcineurin inhibitor. During the first 6 weeks after transplantation, the anti-CD3-stimulated proliferative response of peripheral blood T lymphocytes (PBTL) was studied by cell cycle analysis. The proportion of PBTL in different phases of the cell cycle and expression of IL-2R were determined by flow cytometry. As an effect of quadruple immunosuppressive therapy including IL-2R antagonists, cell cycle analysis showed an incremental decrease in the proliferative response of PBTL during the first 6 weeks after renal transplantation. A sudden drop in the proportion of IL-2R-positive cells was observed immediately after the first dose of the IL-2R antagonist and a significant antiproliferative effect on PBTL after the second dose. In vitro, IL-2R antagonists showed a dose-dependent inhibition of the anti-CD3-stimulated proliferation of PBTL of healthy blood donors. Cell cycle analysis of the immune reactivity of renal allograft recipients may represent a valuable tool for the immunological posttransplant follow-up and optimization of the immunosuppressive therapy.
引用
收藏
页码:191 / 200
页数:10
相关论文
共 37 条
[1]   Efficacy and cardiovascular safety of daclizumab, mycophenolate mofetil, tacrolimus, and early steroid withdrawal in renal transplant recipients: a multicenter, prospective, pilot trial [J].
Abramowicz, D ;
Vanrenterghem, Y ;
Squifflet, JP ;
Kuypers, D ;
Mourad, M ;
Meurisse, M ;
Wissing, M .
CLINICAL TRANSPLANTATION, 2005, 19 (04) :475-482
[2]  
[Anonymous], AM J TRANSPLANT S3
[3]   Comparison of ATP production in whole blood and lymphocyte proliferation in response to phytohemagglutinin [J].
Augustine, Nancy H. ;
Pasi, Brian M. ;
Hill, Harry R. .
JOURNAL OF CLINICAL LABORATORY ANALYSIS, 2007, 21 (05) :265-270
[4]   Inhibition of the IL-15 pathway in anti-CD25 mAb treated renal allograft recipients [J].
Baan, CC ;
van Riemsdijk-Overbeeke, IC ;
Boelaars-van Haperen, MJAM ;
IJzermans, JMN ;
Weimar, W .
TRANSPLANT IMMUNOLOGY, 2002, 10 (01) :81-87
[5]   IL-7 and IL-15 bypass the immunosuppressive action of anti-CD25 monoclonal antibodies [J].
Baan, CC ;
Boelaars-van Haperen, MJAM ;
van Riemsdijk, IC ;
van der Plas, AJ ;
Weimar, W .
TRANSPLANTATION PROCEEDINGS, 2001, 33 (03) :2244-2246
[6]   Clinical Relevance of Immune Monitoring in Solid Organ Transplantation [J].
Daniel, Volker ;
Opelz, Gerhard .
INTERNATIONAL REVIEWS OF IMMUNOLOGY, 2009, 28 (3-4) :155-184
[7]   ACTIVATION OF HUMAN LYMPHOCYTES-T BY CROSSLINKING OF ANTI-CD3 MONOCLONAL-ANTIBODIES [J].
DIXON, JFP ;
LAW, JL ;
FAVERO, JJ .
JOURNAL OF LEUKOCYTE BIOLOGY, 1989, 46 (03) :214-220
[8]  
Dragun D, 2009, CONTRIB NEPHROL, V162, P129, DOI 10.1159/000170845
[9]  
FLETCHER MA, 1997, MANUAL CLIN LAB IMMU, P313
[10]   ACTIVATION OF LYMPHOCYTES-T BY IMMOBILIZED MONOCLONAL-ANTIBODIES TO CD3 - REGULATORY INFLUENCES OF MONOCLONAL-ANTIBODIES TO ADDITIONAL T-CELL SURFACE DETERMINANTS [J].
GEPPERT, TD ;
LIPSKY, PE .
JOURNAL OF CLINICAL INVESTIGATION, 1988, 81 (05) :1497-1505