Lavríková Petra, Sečník Peter, Kubíček Zdenek, Jabor Antonín, Hošková Lenka, Franeková Janka
Department of Laboratory Methods, Institute for Clinical and Experimental Medicine, Vídeňská 1958/9, CZ-14021 Prague, Czech Republic; Third Faculty of Medicine, Charles University, Ruská 87, 100 00 Praha 10, Czech Republic.
Department of Laboratory Methods, Institute for Clinical and Experimental Medicine, Vídeňská 1958/9, CZ-14021 Prague, Czech Republic.
Transpl Immunol. 2018 Oct;50:43-47. doi: 10.1016/j.trim.2018.06.005. Epub 2018 Jun 15.
The aim of the study was to investigate the relationship between tacrolimus (TAC) immunosuppressive treatment and serum concentrations of immunoglobulin heavy/light chain pairs (sHLC) and free light chains (sFLC) in patients after heart transplantation (HTX) and to use these biomarkers to predict the risk of infection in these patients. A total of 88 patients with an immunosuppressive regimen involving tacrolimus who underwent HTX were analyzed over 24 months of follow-up. sFLC and sHLC levels were determined before and at three time points after HTX. TAC concentrations were determined at several time points after HTX, and mean TAC concentrations and areas under the curve (AUCs) of TAC concentration were calculated. Relevant clinical data were obtained from patients' medical records. A larger AUC of TAC was associated with decreases in the concentrations of IgG total (p < 0.05); similarly, cumulative AUC of TAC during 18 post-transplant months correlated inversely with sHLC IgG kappa (r = -0.228, p < 0.05) and IgG total (r = -0.352, p < 0.05). Concentrations of sFLC kappa, sFLC lambda, sHLC IgG kappa, and sHLC IgG total were significantly lower in infected patients (in the 9th month after HTX, all p < 0.05). Combined criteria for increased AUC (greater than the median of 12.9 mg·d/l) and decreased sFLC kappa (less than the median of 12.5 mg/l) correlated with the presence of infection (p < 0.03) in the 9th month after HTX. Ratio of concentration of TAC to sFLC kappa or lambda was significantly higher in infected patients (both p < 0.05). Intensive treatment with tacrolimus after HTX is possibly reflected by decreases in sFLC and sHLC (mainly sHLC IgG). Patients with decreased concentrations of these biomarkers are at increased risk for infection, primarily in the 9th month after HTX, when the concentrations of tacrolimus were the highest.
本研究旨在探讨心脏移植（HTX）术后患者中他克莫司（TAC）免疫抑制治疗与血清免疫球蛋白重/轻链对（sHLC）及游离轻链（sFLC）浓度之间的关系，并利用这些生物标志物预测这些患者的感染风险。对88例接受了含他克莫司免疫抑制方案的HTX患者进行了为期24个月的随访分析。在HTX术前及术后三个时间点测定sFLC和sHLC水平。在HTX术后多个时间点测定TAC浓度，并计算TAC浓度的平均浓度及曲线下面积（AUC）。从患者病历中获取相关临床资料。TAC的AUC较大与总IgG浓度降低相关（p<0.05）；同样，移植后18个月内TAC的累积AUC与sHLC IgG κ（r=-0.228，p<0.05）和总IgG（r=-0.352，p<0.05）呈负相关。感染患者（HTX术后第9个月）的sFLC κ、sFLC λ、sHLC IgG κ和sHLC IgG总量浓度显著降低（均p<0.05）。HTX术后第9个月，AUC升高（大于中位数12.9mg·d/l）和sFLC κ降低（小于中位数12.5mg/l）的联合标准与感染的存在相关（p<0.03）。感染患者中TAC与sFLC κ或λ的浓度比显著更高（均p<0.05）。HTX术后他克莫司的强化治疗可能表现为sFLC和sHLC（主要是sHLC IgG）降低。这些生物标志物浓度降低的患者感染风险增加，主要在HTX术后第9个月，此时他克莫司浓度最高。
