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OP0084 Cardiopathogenic Role of Human RO/SSA and LA/SSA Antibodies Demonstrated in a Novel Animal Model of Congenital Heart Block
  1. A. Hoxha1,
  2. A. Ruffatti1,
  3. V. Ottosson2,
  4. L. Ottosson2,
  5. M. Hedlund2,
  6. T. Del Ross1,
  7. L. Punzi1,
  8. S.-E. Sonesson3,
  9. M. Wahren-Herlenius2
  1. 1Department of Medicine, Rheumatology Unit, University of Padua, Padua, Italy
  2. 2Department of Medicine, Rheumatology Unit
  3. 3Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden

Abstract

Background Congenital atrioventricular block (CHB) depend on Ro/SSA and/or La/SSB-autoantibody mediated inflammation and subsequent fibrosis of the atrioventricular node. Despite the association of maternal Ro/SSA and La/SSB autoantibodes with congenital heart block, the mechanisms involved remain unclear.

Objectives To study the effect on cardiac conduction of purified human IgG antibodies from a CHB patient mother in an animal model.

Methods Female Dark Agouti rats (Charles-Rivers, Germany), 15 weeks old, were injected intra peritoneally with different doses (4 and 2 mg) of IgG purified from a CHB mother tested positive for anti-Ro52-p200 antibodies, a healthy control or with vehicle only on day 7 post mating. The assessment of fetal cardiac function during pregnancy was performed by fetal echocardiography/Doppler recordings at approximately 14 days of pregnancy, and neonatal cardiac function after birth was assessed by ECG recordings within 24 h of birth.

Results Performing echocardiography/Doppler we observed significant bradycardia and AV time prolongation in the group injected with 4 mg patient IgG compared to pups injected with 4 mg control IgG or PBS (p=0.0004 and p=0.001, respectively) as well as a significant prolongation of isovolumetric contraction time (ICT) and ejection time (ET) time (p=0.01 and p=0.007). Furthermore, pups in the group injected with 4 mg patient IgG had a significantly higher myocardial performance index (MPI) (p=0.002) than the group injected with 4 mg control IgG. We did not observe bradycardia and/or prolongation of AV time in the group injected with 2 mg patient IgG. However, a significant prolongation of ICT, isovolumetric relaxation time (IRT) and ET time was observed also in the group injected with 2 mg patient IgG compared to 2 mg control IgG (p=0.0003, p=0.001 and p=0.03, respectively). Further, there was a significant increase of MPI (p=0.002) between groups injected with 2 mg patient and control IgG. The ECGs recordings showed that the pups from the group injected with 4 mg patient IgG present a significant reduction of mean heart rate compared to the group injected with 4 mg control IgG (p<0.0001). Moreover, the pups from the 4 mg patient IgG group present a significant prolongation of the PR and RR intervals compared to the group injected with 4 mg IgG control sera (p<0.0001). There was no bradycardia and/or prolongation of PR and RR interval in the group injected with 2 mg patient IgG.

Conclusions Our data suggest that high levels (4 mg) of Ro/SSA and La/SSA autoantibodies induce bradycardia, AV time prolongation and decrease cardiac performance, accurately mimicking features of the human disease and confirming a role for the autoantibodies in disease pathogenesis. Even at low levels (2 mg) these antibodies cause a decrease in cardiac performance. The data also suggest that an animal model for CHB can be established by a simple technique of passive transfer of human IgG from a patient with a child with CHB. This model will be useful and highly relevant for investigating the pathogenesis of CHB induced by human Ro/La antibodies, and for evaluating novel therapeutic approaches and drugs.

Disclosure of Interest None Declared

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