Congenital heart block caused by maternal autoantibodies anti-SSA/Ro and anti-SSB/La

Authors: M. Podrazil;  J. Bartůňková;  A. Šedivá
Authors‘ workplace: Ústav imunologie UK 2. LF a FN Motol, Praha
Published in: Čes. Revmatol., 16, 2008, No. 4, p. 163-168.
Category: Overview Reports


Neonatal lupus syndrome represents a model of passively acquired autoimmunity caused by specific maternal autoantibodies anti-SSA/Ro a anti-SSB/La, which cross the placenta and are associated with the development of congenital heart block in the fetus and/or a transient rash or various liver and blood cell abnormalites in the newborn. Complete form of congenital heart block is a permanent condition that entails significant morbidity, with nearly all affected infants requiring pacemakers. Perinatal mortality may aprroach up to 20 %. An intensive search is therefore ongoing for the specific etiopathophysiology and for diagnostic markers to approach and treat this disease.

Key words:
congenital heart block, neonatal lupus syndrome, autoantibodies anti-SSA/Ro a anti-SSB/La


1. Friedman DM, Rupel A, Buyon JP. Epidemiology, etiology, detection, and treatment of autoantibody-associated congenital heart block in neonatal lupus. Curr Rheumatol Rep 2007 May; 9(2): 101–8.

2. Michaelsson M, Engle MA. Congenital complete heart block: an international study of the natural history. Cardiovasc Clin 1972; 4: 85–101.

3. Waltuck J, Buyon JP. Autoantibody-associated congenital heart block: outcome in mothers and children. Ann Intern Med 1994; 120: 544–551.

4. Brucato A, Frassi M, Franceschini F, Cimaz R, Faden D, Pisoni MP, et al. Risk of congenital complete heart block in newborns of mothers with anti-Ro/SSA antibodies detected by nterimmunoelectrophoresis: a prospective study of 100 women. Arthritis Rheum 2001; 44: 1832–1835.

5. Buyon JP, Hiebert R, Copel J, et al. Autoimmune-associated congenital heart block: mortality, morbidity, and recurrence rates obtained from a national neonatal lupus registry. J Am Coll Cardiol 1998; 31: 1658–66.

6. Buyon JP, Clancy RM. Dying right to live longer: positing apoptosis as a link between maternal autoantibodies and congenital heart block. Lupus. 2008; 17(2): 86–90.

7. Wolin SL, Cedervall T. The La protein. Annu Rev Biochem 2002; 71: 375–403.

8. Chen X, Wolin SL. The Ro 60 kDa autoantigen: insights into cellular function and role in autoimmunity. J Mol Med 2004; 82: 232–239.

9. Espinosa A, Zhou W, Ek M, Hedlund M, Brauner S, Popovic K, et al. The Sjögren’s syndrome-associated autoantigen Ro52 is an E3 ligase that regulates proliferation and cell death. J Immunol 2006; 176: 6277–6285.

10. Salomonsson S, Dörner T, Theander E, Bremme K, Larsson P, Wahren-Herlenius M. A serologic marker for fetal risk of congenital heart block. Arthritis Rheum 2002; 46:1233–1241.

11. Cooley HM, Keech CL, Melny BJ, et al. Monozygotic twins discordant for congenital complete heart block. Arthritis Rheum 1997; 40: 381–4.

12. Fritsch C, Hoebeke J, Dali H, Ricchiuti V, Isenberg DA, Meyer O, Muller S. 52-kDa Ro/SSA epitopes preferentially recognized by antibodies from mothers of children with neonatal lupus and congenital heart block. Arthritis Res Ther 2005; 8:R4.

13. Clancy RM, Buyon JP, Ikeda K, Nozawa K, Argyle DA, Friedman DM, et al. Maternal antibody responses to the 52-kd SSA/Ro p200 peptide and the development of fetal conduction defects. Arthritis Rheum 2005; 52:3079–3086.

14. Eftekhari P, Salle L, Lezoualc’h F, Mialet J, Gastineau M, Briand JP, et al. Anti- SSA/Ro52 autoantibodies blocking the cardiac 5-HT4 serotoninergic receptor could explain neonatal lupus congenital heart block. Eur J Immunol 2000; 30: 2782–2790.

15. Kamel R, Eftekhari P, Clancy R, Buyon JP, Hoebeke J. Autoantibodies against the serotoninergic 5-HT4 receptor and congenital heart block: a reassessment. J Autoimmun 2005; 25: 72–76.

16. Salomonsson S, Sonesson SE, Ottosson L, Muhallab S, Olsson T, Sunnerhagen M, et al. Ro/SSA autoantibodies directly bind cardiomyocytes, disturb calcium homeostasis, and mediate congenital heart block. J Exp Med 2005; 201: 11–17.

17. Buyon JP, Clancy RM. Autoantibody-associated congenital heart block: TGFbeta and the road to scar. Autoimmun Rev 2005; 4: 1–7.

18. Solomon DG, Rupel A, Buyon JP. Birth order, gender and recurrence rate in autoantibody-associated congenital heart block: implications for pathogenesis and family counseling. Lupus 2003; 12: 646–647.

19. Buyon JP, Hiebert R, Copel J, et al. Autoimmune-associated congenital heart block: mortality, morbidity, and recurrence rates obtained from a national neonatal lupus registry. J Am Coll Cardiol 1998; 31: 1658–66.

20. Julkunen H, Eronen M. Long-term outcome of mothers of children with isolated heart block in Finland. Arthritis Rheum 2001; 44: 647–652.

21. Izmirly PM, Rivera TL, Buyon JP. Neonatal lupus syndromes. Rheum Dis Clin North Am 2007 May; 33(2): 267-85, vi.

22. Skog A, Wahren-Herlenius M, Sundström B, Bremme K, Sonesson SE. Outcome and growth of infants fetally exposed to heart block-associated maternal anti-Ro52/SSA autoantibodies. Outcome and growth of infants fetally exposed to heart block-associated maternal anti-Ro52/SSA autoantibodies. Pediatrics 2008 Apr.; 121(4): e803–9.

23. Glickstein J, Buyon J, Kim M, Friedman D. PRIDE investigators. The fetal Doppler mechanical PR interval: a validation study. Fetal Diagn Ther 2004 Jan-Feb; 19(1): 31–4.

24. Buyon JP, Askanase AD, Kim MY, Copel JA, Friedman DM. Identifying an early marker for congenital heart block: when is a long PR interval too long? Comment on the article by Sonesson et al. Arthritis Rheum 2005 Apr; 52(4): 1341–2.

25. Friedman DM, Kim MY, Copel JA, Davis C, Phoon CK, Glickstein JS, et al. PRIDE investigators: Utility of cardiac monitoring in fetuses at risk for congenital heart block: the PR Interval and Dexamethasone Evaluation (PRIDE) prospective study. Circulation. 2008 Jan 29; 117(4): 485–93. Epub 2008 Jan 14.

26. Blanford AT, Murphy BE. In vitro metabolism of prednisolone, dexamethasone, betamethasone, and cortisol by the human placenta. Am J Obstet Gynecol 1977; Feb 1;127(3): 264–7.

27. Saleeb S, Copel J, Friedman D, et al. Comparison of treatment with fluorinated glucocorticoids to the natural history of autoantibody-associated congenital heart block. Arthritis Rheum 1999; 42: 2335–45.

28. Jaeggi ET, Fouron J-C, Silverman ED, et al. Transplacental fetal treatment improves the outcome of prenatally diagnosed complete atrioventricular block without structural heart disease. Circulation 2004; 110: 1542–8.

29. Breur JMPJ, Visser GHA, Kruizc AA, et al. Treatment of fetal heart block with maternal steroid therapy: case report and review of the literature. Ultrasound Obstet Gynecol 2004; 24: 467–72.

30. Robinson BV, Ettedgui JA, Sherman FS. Use of terbutaline in the treatment of complete heart block in the fetus. Cardiol Young 2001; 11: 683–6.

31. Carpenter RJ Jr, Strasburger JF, Garson A Jr, et al. Fetal ventricular pacing for hydrops secondary to complete atrioventricular block. J Am Coll Cardiol 1986; 8: 1434–6.

32. Van der Leij JN, Visser GH, Bink-Boelkens MT, et al. Successful outcome of pregnancy after treatment of maternal anti-Ro (SSA) antibodies with immunosuppressive therapy and plasmapheresis. Prenat Diagn 1994; 14: 1003–7.

33. Wong JP, Kwek KY, Tan JY, et al. Fetal congenital complete heart block: prophylaxis with intravenous gammaglobulin and treatment with dexamethasone. AustNZ J Obstet Gynaecol 2001; 41: 339–41.

34. Branch DW, Porter TF, Paidas MJ, et al. Obstetric uses of intravenous immunoglobulin: successes, failures and promises. J Allergy Clin Immunol 2001; 108: S133–8.

35. Shinohara K, Miyagawa S, Fujita T, et al. Neonatal lupus erythematosus: results of maternal corticosteroid therapy. Obstet Gynecol 1999; 93: 952–7.

Dermatology & STDs Paediatric rheumatology Rheumatology
Forgotten password

Don‘t have an account?  Create new account

Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.


Don‘t have an account?  Create new account