Schäfer P, Tenschert W, Cremaschi L, Gutensohn K, Laufs R
Institut für Medizinische Mikrobiologie and Immunologie, Universitäts-Krankenhaus Eppendorf, Hamburg, Germany.
J Clin Microbiol. 1998 Apr;36(4):1008-14. doi: 10.1128/JCM.36.4.1008-1014.1998.
The feasibility of the major peripheral blood leukocyte (PBL) subsets for use in qualitative and quantitative PCR to monitor secondary cytomegalovirus (CMV) infection and ganciclovir therapy was assessed with 188 blood samples derived from 40 CMV immunoglobulin G-positive renal-allograft recipients. In pp65 antigen-positive patients all leukocyte fractions, but only 79.5% of plasma preparations, were PCR positive. In pp65 antigen-negative samples from patients after antiviral treatment only 7.3% of polymorphonuclear cell (PMNL) samples, but 81.8% of peripheral blood mononuclear cells (PBMC), and 10.9% of plasma samples remained PCR positive. Similarly, in patients with latent infections only 5.0% of PMNL, but 51.7% of PBMC preparations, and 8.0% of plasma samples were PCR positive. Regarding patients with active CMV infection, CMV DNA copy numbers in PMNL correlated significantly with pp65 antigen-positive cell counts before and after onset of ganciclovir therapy. Significant differences in CMV DNA copy numbers in PMNL and plasma were observed (i) between patients with symptomatic infection and those with asymptomatic infection and (ii) between patients with active infection and those with latent infection. In contrast, PBMC harbored equally low CMV DNA levels both in patients with active infection and those with latent infections, and no decline of CMV DNA load in PBMC was observed during antiviral treatment. We conclude that detection of CMV DNA in PMNL, not in PBMC, is associated with active infections and is more sensitive than detection of CMV DNA in plasma. Negative PCR results for PMNL after antiviral therapy indicate recovery, and fewer unwanted positive results occur compared to PBMC and plasma. Therefore, purified PMNL should be preferred for analysis by qualitative CMV PCR to avoid unwanted positive results. The CMV DNA load in PBMC compared with that in PMNL is negligible during active infection, so mixed PBL are sufficient for use in quantitative PCR.
利用来自40名巨细胞病毒(CMV)免疫球蛋白G阳性肾移植受者的188份血样,评估了主要外周血白细胞(PBL)亚群用于定性和定量PCR以监测继发性CMV感染和更昔洛韦治疗的可行性。在pp65抗原阳性患者中,所有白细胞组分均PCR阳性,但血浆制剂只有79.5%呈PCR阳性。在抗病毒治疗后患者的pp65抗原阴性样本中,只有7.3%的多形核细胞(PMNL)样本呈PCR阳性,但外周血单核细胞(PBMC)有81.8%、血浆样本有10.9%仍呈PCR阳性。同样,在潜伏感染患者中,只有5.0%的PMNL、但51.7%的PBMC制剂以及8.0%的血浆样本呈PCR阳性。对于活动性CMV感染患者,PMNL中的CMV DNA拷贝数与更昔洛韦治疗开始前后的pp65抗原阳性细胞计数显著相关。在PMNL和血浆中的CMV DNA拷贝数方面观察到显著差异:(i)有症状感染患者与无症状感染患者之间;(ii)活动性感染患者与潜伏感染患者之间。相比之下,无论是活动性感染患者还是潜伏感染患者,PBMC中的CMV DNA水平均同样低,并且在抗病毒治疗期间未观察到PBMC中CMV DNA载量下降。我们得出结论,在PMNL而非PBMC中检测CMV DNA与活动性感染相关,并且比在血浆中检测CMV DNA更敏感。抗病毒治疗后PMNL的PCR阴性结果表明已康复,与PBMC和血浆相比,出现的不必要阳性结果更少。因此,纯化的PMNL应优先用于CMV定性PCR分析以避免不必要的阳性结果。在活动性感染期间,PBMC中的CMV DNA载量与PMNL中的相比可忽略不计,因此混合的PBL足以用于定量PCR。