Objective:To investigate the relationship between the levels of serum cytokines and chemokines and the prognosis of patients with acute B-ALL after receiving chimeric antigen receptor (CAR)-T cell immunotherapy and acute graft-versus-host disease (aGVHD) in patients after bridging allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:According to the case-control principle, Forty-two patients with B-ALL who received CD19-CAR-T cell immunotherapy bridged to allo-HSCT at Heibei Yanda Ludaopei Hospital from September 18, 2019 to May 9, 2022 were enrolled. Mann-Whitney U test was used to compare the changes of aGVHD-related cytokines and chemokine levels between CAR-T cell immunotherapy and bridging transplantation in different patients at the same time. Their plasma levels of cytokines and chemokines related to aGVHD were monitored at the day before CAR-T therapy and after CAR-T treatment at day 4, 7,14,21,28. The receiver operating characteristic curve was drawn to evaluate the predictive value of cytokines and chemokines in predicting the occurrence and the death of aGVHD patients. Kaplan-Meier method and Log-rank tests were used for Overall survival (OS) analysis. Results:Twenty-four of total 42 patients had aGVHD, of which 11 patients died and 31 patients survived. There was no significant difference in cytokines and chemokines between the aGVHD group and the non-aGVHD group on the day before CAR-T cell treatment. According to statistical analysis, the serum Elafin levels of aGVHD group was higher than that of non-aGVHD group at the 21st day [4 482 (2 811, 6 061) ng/L vs 2 466 (1 948, 3 375) ng/L, Z=3.145, P=0.001] and the 28st day [4 391 (2 808, 5594) ng/L vs 2 463 (1 658, 2 830) ng/L, Z=2.038, P=0.048] separately. At the 14th day, serum cytokines and chemokines levels between the two group were as follows,MIP-1 α [21.02 (12.36, 30.35) ng/L vs 5.56 (3.64, 10.79) ng/L], sCD25 [422.47 (257.99, 1 233.78) IU/ml vs 216.11 (133.75,457.39) IU/ml], Elafin [4 101 (2 393, 5 006) ng/L vs 2 155 (1 781, 3 033) ng/L], IL-6 [119.08 (23.97, 183.43) ng/L vs 8.39 (2.91, 17.42) ng/L] and IL-8 [13.56 (12.50, 24.52) ng/L vs 2.83 (1.73,6.87) ng/L] were at higher levels ( Z=2.653, P=0.007; Z=2.176, P=0. 030; Z=2.058, P=0.041; Z=3.329, P<0.001; Z=3.162, P=0.001). The KM survival curve showed that the cumulative survival rates of patients with higher serum levels of MIP-1α, sCD25, Elafin, IL-6 and IL-8 were lower than those with low levels at day 14, and the difference was statistically significant (χ 2=12.353, 4.890, 6.551, 10.563, 20.755, P<0.05). Conclusion:The outcomes of patients treated with CAR-T cell therapy bridged to allo-HSCT was correlated with serum MIP-1α, sCD25, Elafin, IL-6 and IL-8 levels after receiving CAR-T therapy. High concentrations of MIP-1α, sCD25, Elafin, IL-6 and IL-8 suggest poor prognosis and can be used as biomarkers to suggest appropriate clinical selection of therapy.

目的 探讨改良中性粒细胞CD64(nCD64)指数与传统nCD64指数鉴别诊断感染的临床应用效能差异.方法 纳入自身免疫性疾病(AID)患者32例、血液肿瘤患者32例、急诊发热患者59例及健康体检者41例.所有患者中确诊感染者76例,非感染者47例.采用流式细胞术检测外周血淋巴细胞、单核细胞和中性粒细胞的CD64荧光强度,计算改良nCD64指数和传统nCD64指数并比较两种指数对感染的鉴别诊断效能.结果 感染患者的改良nCD64指数和传统nCD64指数均显著高于非感染患者及健康体检者(均P<0.05);两种指数鉴别感染的AUC分别为0.782和0.770(均P<0.05),最佳临界值分别为1.00和4.74.传统指数仅在AID中具有较好的诊断效能(AUC=0.887,P<0.05),改良指数在三类患者中均有较好的诊断效能(AUC均>0.75,P<0.05).结论 两种nCD64指数对感染的鉴别诊断均有一定的临床价值,且二者在自身免疫性疾病中诊断价值最高,改良nCD64指数较传统nCD64指数在急诊发热患者和血液肿瘤中有更高的诊断效能.

Objective:To explore the efficacy and safety of pretreating with oral immunosuppressants alone for ABO-incompatible (ABOi) renal transplant recipients with an initial isoagglutinin titer <1: 8.Methods:From September 2014 to October 2019, 16 cases of ABOi renal transplantation pretreated with oral immunosuppressants alone and 32 cases of ABO-compatible (ABOc) renal transplantation were recruited for comparing the inter-group incidence of graft function, acute rejection, infection and recipient and allograft survival.Results:The 16 ABOi renal transplantations were AB-to-A(n=4), AB-to-B(n=3), A-to-B(n=1), B-to-A(n=4), A-to-O(n=2) and B-to-O(n=2). The initial isoagglutinin titer (IgM & IgG) and that on the date of transplantation were both ≤1∶8. The median follow-up period was 495(90-1696) days. One patient in ABOi group underwent allograft nephrectomy due to hyperacute rejection. The graft survival rates were 93.75%(15/16) and 100%(32/32) in ABOi and ABOc groups respectively. No recipient died. No significant inter-group difference existed in postoperative renal function after 6 months (serum creatinine μmol/L: 114.30±28.13 vs. 106.08±23.80, P=0.38; eGFR ml/min/1.73 m 2: 64.93±19.60 vs. 82.34±22.58, P=0.13). In ABOi group, there were 3 episodes of postoperative infection, 2 episodes of acute rejection within 2 weeks (including 1 episode of hyperacute rejection) and 1 episode of acute rejection after 2 weeks; 5 episodes of postoperative infection, no acute rejection within 2 weeks and 5 episodes of acute rejection after 2 weeks in ABOc group. No significant inter-group difference existed in the incidence of infection or rejection ( P>0.05). Conclusions:Using oral immunosuppressant alone is both safe and feasible for ABOi renal transplantation recipients with an initial isoagglutinin titer ≤1∶8. It may greatly simplify the pretreatment scheme for those with a low initial isoagglutinin titer and lower the incidence of complications.

目的 验证全自动间接免疫荧光法分析仪(HELIOS)的判读系统检测抗核抗体(ANA)与人工判读结果的一致性并依据其系统功能与评价结果分析其在临床实验中的应用.方法 分别用HELIOS自动判读系统和通过荧光显微镜对2015年2月281例门诊及住院患者的ANA荧光载片进行判读,HELLOS只能判定滴度,不能判定荧光核型,故仅对标本的阴阳性及阳性结果的滴度进行统计学分析.结果 HELIOS的判读系统与人工判读阴阳性结果之间的差异无统计学意义(P＞0.05),总符合率为98.9％,阳性符合率为99.5％,阴性符合率为97.4％,一致性检验kappa值为0.973.HELLOS判读与人工判读的各滴度之间的差异无统计学意义(P＞0.05).结论 HELIOS的判读系统与人工判读结果的一致性较好,HELIOS自动化程度高,操作简单,结果可靠性好,适用于临床推广使用.

At present,transplantation has been the predominant way to solve most of the end-stage diseases,ensued by the use of immunosuppressive drugs.Since the immunosuppressive drugs have narrow therapeutic index,the blood drug concentration is needed to mornior.Pharmacogenetics is one subject which focuses on the interaction between gene and the metabolism of the drug,providing great help for designing the regime of achieving the target drug concentration.Meanwhile,it facilitates the realization of individual therapy.This review thus focuses on the latest advancement on the pharmacogenetics of those immunosupprressants,hoping to provide help for the treatment.