Clinical use of an immune monitoring panel in liver transplant recipients: A prospective, observational study

被引:2
作者
Iovino, Lorenzo [1 ,2 ,3 ]
Taddei, Riccardo [4 ]
Bindi, Maria Lucia [4 ]
Morganti, Riccardo [5 ]
Ghinolfi, Davide [6 ]
Petrini, Mario [1 ]
Biancofiore, Gianni [4 ]
机构
[1] Univ Sch Med, Hematol Div, Via Roma, I-56100 Pisa, Italy
[2] Fred Hutchinson Canc Res Ctr, Clin Res Div, Program Immunol, 1124 Columbia St, Seattle, WA 98104 USA
[3] Fred Hutchinson Canc Res Ctr, Immunotherapy Integrated Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA
[4] Univ Sch Med, Azienda Osped Univ Pisana, Transplant Anesthesia & Crit Care, Via Paradisa 2, I-56100 Pisa, Italy
[5] Univ Sch Med, Dept Clin & Expt Med, Via Roma, I-56100 Pisa, Italy
[6] Univ Sch Med, Azienda Osped Univ Pisana, Liver Transplant Surg, Via Paradisa 2, I-56100 Pisa, Italy
关键词
Liver transplant; Immune monitoring; Infections; Graft rejection; Immune suppression; NATURAL-KILLER-CELLS; HEPATITIS-C; INFECTIOUS COMPLICATIONS; IMMUNOSUPPRESSIVE DRUGS; CALCINEURIN INHIBITORS; ALLOGRAFT-REJECTION; PERIPHERAL-BLOOD; THERAPY; HYPOGAMMAGLOBULINEMIA; INDUCTION;
D O I
10.1016/j.trim.2018.11.001
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Immunosuppressive therapy greatly contributed to making liver transplantation the standard treatment for end stage liver diseases. However, it remains difficult to predict and measure the efficacy of pharmacological immunosuppression. Therefore, we used a panel of standardized, commonly available, biomarkers with the aim to describe their changes in the first 3 weeks after the transplant procedure and assess if they may help therapeutic drug monitoring in better tailoring the dose of the immunosuppressive drugs. We prospectively studied 72 consecutive patients from the day of liver transplant (post-operative day #0) until the post-operative day #21. Leukocytes, neutrophils, lymphocytes (CD4+, CD8+), natural killer cells, monocytes, immunoglobulins and tacrolimus serum levels were measured on peripheral blood (at day 0, 3, 7, 14, 21 after surgery). Patients who developed infections showed significantly higher CD64+ monocytes on post operative day #7. IgG levels were lower on post operative day #3 among patients who later developed infections. We also found that a sharp decrease in IgA from post operative day #0 to 3 (226 mg/dL in the ROC curve analysis) strongly correlates with the onset of infections among HCV patients. No specific markers of rejection emerged from the tested panel of markers. Our results show that some early changes in peripheral blood white cells and immunoglobulins may predict the onset of infections and may be useful in modulating the immunosuppressive therapy. However, a panel of commonly available, standardized biomarkers do not support in improving therapeutic drug monitoring ability to individualize immunosuppressive drugs dosing.
引用
收藏
页码:45 / 52
页数:8
相关论文
共 54 条
[1]   From immunosuppression to tolerance [J].
Adams, David H. ;
Sanchez-Fueyo, Alberto ;
Samuel, Didier .
JOURNAL OF HEPATOLOGY, 2015, 62 :S170-S185
[2]   Production of Proinflammatory Cytokines by Monocytes in Liver-Transplanted Recipients with De Novo Autoimmune Hepatitis Is Enhanced and Induces TH1-like Regulatory T Cells [J].
Arterbery, Adam S. ;
Osafo-Addo, Awo ;
Avitzur, Yaron ;
Ciarleglio, Maria ;
Deng, Yanhong ;
Lobritto, Steven J. ;
Martinez, Mercedes ;
Hafler, David A. ;
Kleinewietfeld, Markus ;
Ekong, Udeme D. .
JOURNAL OF IMMUNOLOGY, 2016, 196 (10) :4040-4051
[3]   Clinical factors affecting rejection rates in liver transplantation [J].
Au, Kin Pan ;
Chan, See-Ching ;
Chok, Kenneth Siu-Ho ;
Sharr, William Wei ;
Dai, Wing-Chiu ;
Sin, Sui-Ling ;
Wong, Tiffany Cho-Lam ;
Lo, Chung-Mau .
HEPATOBILIARY & PANCREATIC DISEASES INTERNATIONAL, 2015, 14 (04) :367-373
[4]   Neurotoxicity of calcineurin inhibitors: impact and clinical management [J].
Bechstein, WO .
TRANSPLANT INTERNATIONAL, 2000, 13 (05) :313-326
[5]   Mitigating Risk of Immunosuppression by Immune Monitoring: Are We There? [J].
Bentall, Andrew ;
Amer, Hatem .
TRANSPLANTATION, 2018, 102 (03) :349-350
[6]   Barcelona Consensus on Biomarker-Based Immunosuppressive Drugs Management in Solid Organ Transplantation [J].
Brunet, Merce ;
Shipkova, Maria ;
van Gelder, Teun ;
Wieland, Eberhard ;
Sommerer, Claudia ;
Budde, Klemens ;
Haufroid, Vincent ;
Christians, Uwe ;
Lopez-Hoyos, Marcos ;
Barten, Markus J. ;
Bergan, Stein ;
Picard, Nicolas ;
Millan Lopez, Olga ;
Marquet, Pierre ;
Hesselink, Dennis A. ;
Noceti, Ofelia ;
Pawinski, Tomasz ;
Wallemacq, Pierre ;
Oellerich, Michael .
THERAPEUTIC DRUG MONITORING, 2016, 38 :S1-S20
[7]   Neutrophils: a cornerstone of liver ischemia and reperfusion injury [J].
Caldeira de Oliveira, Thiago Henrique ;
Marques, Pedro Elias ;
Proost, Paul ;
Teixeira, Mauro Martins M. .
LABORATORY INVESTIGATION, 2018, 98 (01) :51-62
[8]   Rationale of personalized immunosuppressive medication for hepatocellular carcinoma patients after liver transplantation [J].
Chen, Kan ;
Man, Kwan ;
Metselaar, Herold J. ;
Janssen, Harry L. A. ;
Peppelenbosch, Maikel P. ;
Pan, Qiuwei .
LIVER TRANSPLANTATION, 2014, 20 (03) :261-269
[9]  
Choudhary NS, 2017, J CLIN EXP HEPATOL, V7, P358, DOI 10.1016/j.jceh.2017.10.003
[10]   Regulatory T cell therapy: An option to induce operational tolerance in liver transplantation [J].
Conti, F. ;
Dahlqvist, G. ;
Brisson, H. ;
Miyara, M. ;
Calmus, Y. ;
Gorochov, G. .
CLINICS AND RESEARCH IN HEPATOLOGY AND GASTROENTEROLOGY, 2016, 40 (06) :660-665