Cellular mechanism of the conduction abnormalities induced by serum from anti-Ro/SSA-positive patients in rabbit hearts.
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.
Garcia
S
S
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil.
Nascimento
J H
JH
Bonfa
E
E
Levy
R
R
Oliveira
S F
SF
Tavares
A V
AV
de Carvalho
A C
AC
D000818:Animals; D001323:Autoantibodies / Q000097:blood* / Q000494:pharmacology*; D001324:Autoantigens / Q000276:immunology*; D002478:Cells, Cultured; D004562:Electrocardiography / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006329:Heart Conduction System / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood* / Q000494:pharmacology*; D066298:In Vitro Techniques; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D008564:Membrane Potentials / Q000187:drug effects; D020733:RNA, Small Cytoplasmic; D011817:Rabbits; D012261:Ribonucleoproteins / Q000276:immunology*; D000097585:SS-B Antigen; D000099207:SS-A Antigen
D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G; D020733:RNA, Small Cytoplasmic; D012261:Ribonucleoproteins; D000097585:SS-B Antigen; D000099207:SS-A Antigen; C116006:RO60 protein, human