Garcia S, Nascimento J H, Bonfa E, Levy R, Oliveira S F, Tavares A V, de Carvalho A C
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil.
J Clin Invest. 1994 Feb;93(2):718-24. doi: 10.1172/JCI117025.
In this study, IgG fractions from sera of SLE patients with anti-Ro/SSA or anti-Ro/SSA and anti-La/SSB activity were tested in Langendorff preparations of adult rabbit hearts, aiming to reproduce the cardiac manifestations observed in neonatal lupus in an experimental model. The hearts were perfused with normal Tyrode's solution for 30 min, followed by perfusion with Tyrode's containing 0.3 mg/ml of anti-Ro/SSA- (or anti-Ro/La-) positive IgG (nine sera), anti-ribonucleoprotein (RNP)-positive IgG (five sera), or IgG fractions from normal donors (five sera). In one third of the experiments done with anti-Ro/La-positive IgG, heart block was observed. With the remaining fractions, a decrease in heart rate of 17.1% was observed, but normal sinus rhythm was maintained. The IgG fractions with anti-RNP activity (five experiments) and from normal sera (six experiments) reduced heart rates by 12.9 and 3.3%, respectively, but heart block was not observed. To further characterize the cellular mechanisms involved in the conduction disturbances observed in the whole rabbit hearts, we conducted experiments with ventricular myocytes isolated from young rabbit hearts, studied by whole cell patch-clamp technique. In these experiments, the slow inward currents were analyzed during the superfusion of the cell with normal Tyrode's solution and 5 min after superfusion with Tyrode's solution containing 0.3 mg/ml of anti-Ro/SSA- (or anti-Ro/La-) positive IgG (five sera), anti-RNP-positive IgG (three sera), or IgG from normal donors (four sera). Resting and action potential amplitudes were not affected by any of the sera used. The anti-Ro/SSA IgG fraction induced a mean reduction in the peak slow inward current of 31.6%. IgG fractions with anti-RNP activity reduced slow inward current by 4.4%, whereas IgG fractions from normal donors increased this current by 3.3%. IgG-free fractions from sera of patients with anti-Ro/SSA activity did not alter the peak slow inward current. These results show, for the first time, that the presence of anti-Ro/SSA or anti-Ro/SSA and anti-La/SSB antibody activity in IgG fractions from lupus patients' sera can induce cardiac conduction disorders similar to those observed in neonatal lupus.
在本研究中，对具有抗Ro/SSA或抗Ro/SSA及抗La/SSB活性的系统性红斑狼疮（SLE）患者血清中的IgG组分，在成年兔心脏的Langendorff标本中进行检测，旨在在实验模型中重现新生儿狼疮中观察到的心脏表现。心脏先用正常的台氏液灌注30分钟，然后用含0.3mg/ml抗Ro/SSA（或抗Ro/La）阳性IgG（9份血清）、抗核糖核蛋白（RNP）阳性IgG（5份血清）或正常供体的IgG组分（5份血清）的台氏液灌注。在用抗Ro/La阳性IgG进行的三分之一实验中，观察到了心脏传导阻滞。使用其余组分时，观察到心率下降了17.1%，但窦性心律维持正常。具有抗RNP活性的IgG组分（5次实验）和来自正常血清的IgG组分（6次实验）分别使心率降低了12.9%和3.3%，但未观察到心脏传导阻滞。为了进一步表征在整个兔心脏中观察到的传导障碍所涉及的细胞机制，我们对从幼兔心脏分离的心室肌细胞进行了实验，采用全细胞膜片钳技术进行研究。在这些实验中，在细胞用正常台氏液灌注期间以及用含0.3mg/ml抗Ro/SSA（或抗Ro/La）阳性IgG（5份血清）、抗RNP阳性IgG（3份血清）或正常供体的IgG（4份血清）的台氏液灌注5分钟后，分析缓慢内向电流。静息电位和动作电位幅度均不受所用任何血清的影响。抗Ro/SSA IgG组分使缓慢内向电流峰值平均降低了31.6%。具有抗RNP活性的IgG组分使缓慢内向电流降低了4.4%，而来自正常供体的IgG组分使该电流增加了3.3%。具有抗Ro/SSA活性的患者血清中的无IgG组分未改变缓慢内向电流峰值。这些结果首次表明，狼疮患者血清的IgG组分中存在抗Ro/SSA或抗Ro/SSA及抗La/SSB抗体活性可诱发与新生儿狼疮中观察到的类似的心脏传导障碍。
