体液免疫在扩张型心肌病患者心脏功能障碍中的潜在作用。

Potential role of humoral immunity in cardiac dysfunction of patients suffering from dilated cardiomyopathy.

作者信息

Staudt Alexander, Staudt Yvonne, Dörr Marcus, Böhm Marco, Knebel Fabian, Hummel Astrid, Wunderle Lydia, Tiburcy Malte, Wernecke Klaus D, Baumann Gert, Felix Stephan B

机构信息

Klinik für Innere Medizin B, Ernst-Moritz-Arndt-Universität, Greifswald, Germany.

出版信息

J Am Coll Cardiol. 2004 Aug 18;44(4):829-36. doi: 10.1016/j.jacc.2004.04.055.

DOI:10.1016/j.jacc.2004.04.055

PMID:15312867

Abstract

OBJECTIVES

This research was conducted to evaluate the role played by the humoral immune system in cardiac dysfunction among dilated cardiomyopathy (DCM) patients, as enabled by immunoadsorption therapy (IA) that effectively removes functionally active cardiac autoantibodies from plasma.

BACKGROUND

Various circulating autoantibodies have been detected among patients suffering from DCM.

METHODS

Before IA, antibodies were purified from plasma of 45 DCM patients (left ventricular ejection fraction [LVEF] <30%). We analyzed the functional effects of antibodies (300 mg/l) on calcium transients and on systolic cell shortening in adult rat cardiomyocytes. After this in vitro analysis, IA was performed in four courses at one-month intervals until month 3.

RESULTS

Antibodies from 29 patients induced a reduction (>10%) in calcium transients (mean reduction: -16.5 +/- 1.9%) and a simultaneous reduction (>10%) of cell shortening (mean reduction: -21.2 +/- 1.8%) on cardiomyocytes (p < 0.001) (cardiodepressant group). Antibodies from 16 patients did not significantly influence calcium transients and cell shortening (<10%) (non-cardiodepressant group). During the first IA course, the cardiodepressant group demonstrated an acute increase in cardiac index (CI) from 2.2 +/- 0.1 l/min/m(2) to 2.9 +/- 0.1 l/min/m(2) (p < 0.001). In the non-cardiodepressant group, hemodynamics did not significantly change throughout three months. After three months before the final IA course (prolonged effects), the CI was 2.1 +/- 0.1 l/min/m(2) in the non-cardiodepressant group and 2.9 +/- 0.1 l/min/m(2) in the cardiodepressant group (p < 0.001). After three months LVEF increased only in the cardiodepressant group: from 20.8 +/- 1% to 30.5 +/- 1% (p < 0.01).

CONCLUSIONS

In the majority of DCM patients, disturbances of humoral immunity with production of cardiodepressant antibodies may play a functional role in cardiac dysfunction. Evidence of cardiodepressant antibodies predicts hemodynamic benefits during IA.

摘要

目的

本研究旨在评估体液免疫系统在扩张型心肌病（DCM）患者心脏功能障碍中所起的作用，这是通过免疫吸附疗法（IA）实现的，该疗法可有效从血浆中去除具有功能活性的心脏自身抗体。

背景

在DCM患者中已检测到多种循环自身抗体。

方法

在进行IA之前，从45例DCM患者（左心室射血分数[LVEF]<30%）的血浆中纯化抗体。我们分析了抗体（300mg/l）对成年大鼠心肌细胞钙瞬变和收缩期细胞缩短的功能影响。在这项体外分析之后，每隔一个月进行四个疗程的IA，直至第3个月。

结果

29例患者的抗体导致心肌细胞钙瞬变降低（>10%）（平均降低：-16.5±1.9%），同时细胞缩短降低（>10%）（平均降低：-21.2±1.8%）（p<0.001）（心脏抑制组）。16例患者的抗体对钙瞬变和细胞缩短没有显著影响（<10%）（非心脏抑制组）。在第一个IA疗程期间，心脏抑制组的心脏指数（CI）从2.2±0.1l/min/m²急性增加到2.9±0.1l/min/m²（p<0.001）。在非心脏抑制组中，整个三个月血流动力学没有显著变化。在最后一个IA疗程前三个月（长期效应），非心脏抑制组的CI为2.1±0.1l/min/m²，心脏抑制组为2.9±0.1l/min/m²（p<0.001）。三个月后，仅心脏抑制组的LVEF增加：从20.8±1%增加到30.5±1%（p<0.01）。