Freimark D, Czer L S, Aleksic I, Ruan X M, Admon D, Blanche C, Trento A, Fishbein M C
Division of Cardiology, Cedars-Sinai Medical Center, Los Angeles, Calif 90048, USA.
J Heart Lung Transplant. 1995 Nov-Dec;14(6 Pt 1):1197-203.
Endocardial lymphocytic infiltrates, known as Quilty effect, are a common finding of uncertain pathogenesis in cardiac allografts. Quilty effect was not observed before the use of cyclosporine A for immunosuppression and is not generally regarded as a manifestation of rejection. We hypothesized that the endocardial localization of Quilty effect may be related to a relative absence of cyclosporine A in this region.
We used an indirect immunofluorescence staining method with rabbit polyclonal anti-cyclosporine A antibodies to detect cyclosporine A in fresh frozen sections of 27 cardiac allograft endomyocardial biopsies. Staining was graded 0 to +3. Negative controls were from untreated transplant candidates and from biopsies with the primary antibody omitted.
On comparison of endocardial and myocardial fluorescence in biopsy specimens from patients treated with cyclosporine A, there was less endocardial (0.7 +/- 1.1, p < 0.0001) than myocardial (2.2 +/- 0.5) staining. However, in biopsy specimens with Quilty effect (n = 12), this difference was significantly greater (endocardial = 0.2 +/- 0.6 versus myocardial = 2.3 +/- 0.5; p = 0.005) than in specimens without Quilty effect (n = 10) (endocardial = 1.4 +/- 1.2 versus myocardial = 2.1 +/- 0.6; p = 0.7). Endocardial thickness as measured by ocular micrometry was significantly greater in regions with (32 +/- 19 microns) than without (7 +/- 4 microns) Quilty effect, with involved regions showing increased connective tissue (p < 0.0001). In patients with and without Quilty effect, no differences in donor or recipient demographics, prevalence of diabetes, or plasma cyclosporine A levels were found.
Although it has been postulated that Quilty effect is due to the presence of cyclosporine A in cardiac tissue (toxic effect or immunologic reaction), these data suggest that Quilty effect is related to reduced endocardial presence of cyclosporine A, leading to localized, contained, and usually not clinically significant endocardial rejection.
心内膜淋巴细胞浸润，即所谓的奎尔蒂效应，是心脏移植中常见的一种发病机制不明的现象。在使用环孢素A进行免疫抑制之前未观察到奎尔蒂效应，且一般不将其视为排斥反应的表现。我们推测奎尔蒂效应的心内膜定位可能与该区域相对缺乏环孢素A有关。
我们使用兔多克隆抗环孢素A抗体的间接免疫荧光染色方法，在27例心脏移植心内膜心肌活检的新鲜冰冻切片中检测环孢素A。染色分为0至+3级。阴性对照来自未经治疗的移植候选者以及省略一抗的活检标本。
在用环孢素A治疗的患者活检标本中，比较心内膜和心肌的荧光，心内膜染色（0.7±1.1，p<0.0001）少于心肌染色（2.2±0.5）。然而，在有奎尔蒂效应的活检标本（n = 12）中，这种差异（心内膜=0.2±0.6，心肌=2.3±0.5；p = 0.005）比无奎尔蒂效应的标本（n = 10）（心内膜=1.4±1.2，心肌=2.1±0.6；p = 0.7）显著更大。用目镜测微计测量，有奎尔蒂效应的区域（32±19微米）的心内膜厚度显著大于无奎尔蒂效应的区域（7±4微米），受累区域显示结缔组织增加（p<0.0001）。在有和无奎尔蒂效应的患者中，供体或受体人口统计学、糖尿病患病率或血浆环孢素A水平均未发现差异。
尽管有人推测奎尔蒂效应是由于心脏组织中环孢素A的存在（毒性作用或免疫反应），但这些数据表明奎尔蒂效应与心内膜中环孢素A含量降低有关，导致局限性、可控性且通常无临床意义的心内膜排斥反应。
