Department of Clinical and Toxicological Analysis, Faculty of Pharmacy - Federal University of Minas Gerais, Avenida Antonio Carlos, 6627, Pampulha, Belo Horizonte, Minas Gerais, 31270901, Brazil.
Department of Pediatrics, Faculty of Medicine - Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Immunol Res. 2020 Oct;68(5):246-254. doi: 10.1007/s12026-020-09147-3.
Cytokine polymorphisms can influence their plasma levels and thus affect the immune response in renal transplantation. A total of 146 renal transplant recipients (RTR) were classified into groups according to the estimated glomerular filtration rate (R1: < 60 and R2: ≥ 60 mL/min/1.73 m) and time after transplantation (T1: 1 to 24, T2: 25 to 60, T3: 61 to 120, and T4: > 120 months after transplantation). The polymorphisms were genotyped by single specific primer-polymerase chain reaction. IL-10 was measured by ELISA and IL-6, and TNF levels were determined using Miliplex®. A higher frequency of the - 308G allele and the - 308G/G genotype, low-producer, was observed in the R1 group compared with R2. In addition, a higher frequency of the - 308A carriers, high-producer, was found in the R2 group. However, no significant difference was observed in cytokine levels when both groups were compared. Higher levels of IL-6 were observed in T1 compared with T2 and T4 groups. Lower IL-6 levels were found in T2 compared with T3 group. Lower levels of IL-10 were also found in T1 group in relation to T2, while higher levels of this cytokine were observed in T2 group compared with T3. The results suggest that the - 308G > A polymorphism in the TNF gene is associated with filtration function after renal transplantation, and IL-6 and IL-10 levels change according to the time after transplantation. Thus, the joint evaluation of - 308G > A polymorphism in TNF gene and IL-6 and IL-10 levels would provide a broader and effective view on the clinical monitoring of RTR.
细胞因子多态性可影响其血浆水平,从而影响肾移植中的免疫反应。将 146 例肾移植受者(RTR)根据肾小球滤过率估计值(R1:<60 和 R2:≥60 mL/min/1.73 m)和移植后时间(T1:1 至 24,T2:25 至 60,T3:61 至 120,T4:>120 个月)进行分组。通过单特异性引物聚合酶链反应对多态性进行基因分型。通过 ELISA 测定 IL-10,通过 Miliplex®测定 IL-6 和 TNF 水平。与 R2 组相比,R1 组中-308G 等位基因和低产者-308G/G 基因型的频率更高。此外,R2 组中-308A 携带者(高产者)的频率更高。然而,当比较两组时,细胞因子水平没有差异。与 T2 和 T4 组相比,T1 组的 IL-6 水平更高。与 T3 组相比,T2 组的 IL-6 水平更低。与 T2 组相比,T1 组的 IL-10 水平也更低,而 T2 组的这种细胞因子水平更高。结果表明,TNF 基因中的-308G>A 多态性与肾移植后的滤过功能有关,并且 IL-6 和 IL-10 水平根据移植后时间而变化。因此,TNF 基因-308G>A 多态性与 IL-6 和 IL-10 水平的联合评估将为 RTR 的临床监测提供更广泛有效的观点。