Spectrum and progression of conduction abnormalities in infants born to mothers with anti-SSA/Ro-SSB/La antibodies

Abstract

The classic cardiac manifestation of neonatal lupus is congenitalheart block, attributed to antibodymediated inflammation and subsequent fibrosis of the atrioventricular(AV) node. In consideringthe pathologic process of injury it may be that tissue damage results in a range of conduction abnormalities. Identification of less-advanced degrees of block or of fibrosis around the AV node without any conduction abnormality on EKG would support this pathologic model, and serve as a potential marker for treatment if the conduction defect could be shown to progress. To ascertain the spectrum of arrhythmias associated with maternal anti-SSA/Ro-SSB/La antibodies, records of all children enrolled in the Research Registry for Neonatal Lupus were reviewed. Of 187 children with congenital heart block whose mothers have anti-SSA/Ro-SSB/La antibodies, nine had a prolonged PR interval on EKG at birth, four of whom progressed to more advanced AV block. A child whose younger sibling had third degree block was diagnosed with first degree block at age 10 years at the time of surgery for a broken wrist. Two children diagnosed in utero with second degree block were treated with dexamethasone and reverted to normal sinus rhythm by birth, but ultimately progressed to third degree block. Four children had second degree block at birth: of these, two progressed to third degree block. Sinus bradycardia (< 100 bpm) was present in three (3.8%) of 78 fetuses for whom atrial rates were recorded by echocardiogram. Of 40 neonates for whom EKGs were available, the mean atrial rate was 137± 20 bpm (range 75–200). These data have important research and clinical implications. In contrast to the AV node, permanent sinoatrial nodal involvement is not clinically apparent. Perhaps many fetuses sustain mild inflammation, but resolution is variable, as suggested by the presence of incomplete AV block. Since subsequent progression of less-advanced degrees of block can occur, an EKG should be performed on all infants born to mothers with anti-SSA/Ro-SSB/La antibodies.

Keywords

SSA/Ro SSB/La congenital heart block conduction abnormalities neonatal lupus syndromes

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References

Lee LA . Maternal autoantibodies and pregnancy-II: the neonatal lupus syndrome. In: Parke AL (ed). Baillière's Clinical Rheumatology: Pregnancy and the Rheumatic Diseases. Bailliere Tindall: London , 1990, pp 69–84.

Ramsey-Goldman R , Hom D , Deng J-S et al. Anti-SS-A antibodies and fetal outcome in maternal systemic lupus erythematosus . Arthritis Rheum 1986; 29: 1269–1273 .

Lockshin MD , Bonfa E , Elkon K , Druzin ML . Neonatal risk to newborns of mothers with systemic lupus erythematosus . Arthritis Rheum 1988; 31: 697–701 .

Brucato A , Frassi M , Franceschini F et al. Congenital heart block risk to newborns of mothers with anti-Ro/SSA antibodies detected by counterimmunoelectrophoresis. A prospective study of 100 women . Arthritis Rheum 2001; 44: 1832–1835 .

Buyon JP . Neonatal lupus syndrome. In: Lahita R (ed). Systemic lupus erythematosus, 3rd edn. Academic Press: New York , 1998, pp 337–359.

Ben-Chetrit E , Gandy BJ , Tan EM , Sullivan KF . Isolation and characterization of a cDNA clone encoding the 60-kDa component of the human SS-A/Ro ribonucleoprotein autoantigen . J Clin Invest 1989; 83: 1284–1292 .

Deutscher SL , Harley JB , Keene JD . Molecular analysis of the 60 kDa human Ro ribonucleoprotein . Proc Natl Acad Sci USA 1988; 85: 9479–9483 .

Chan EKL , Hamel JC , Buyon JP , Tan EM . Molecular definition and sequence motifs of the 52-kDa component of human SS-A/Ro autoantigen . J Clin Invest 1991; 87: 68–76 .

Itoh K , Itoh Y , Frank MB . Protein heterogeneity in the human Ro/SSA ribonucleoproteins . J Clin Invest 1991; 87: 177–186 .

10.

Chambers JC , Kenan D , Martin BJ , Keene JD . Genomic structure and amino acid sequence domains of the human La autoantigen . J Biol Chem 1988; 263: 18043–18051 .

11.

Miranda-Carus ME , Tseng CE , Rashbaum W , Ochs RL , Casiano CA , Di Donato F , Chan EKL , Buyon JP . Accessibility of SSA/Ro and SSB/La antigens to maternal autoantibodies in apoptotic human fetal cardiac myocytes . J Immunol 1998; 161: 5061–5069 .

12.

Miranda-Carús ME , Dinu Askanase A , Clancy RM , Di Donato F , Chou TM , Libera MR , Chan EKL , Buyon JP . Anti-SSA/Ro and anti-SSB/La autoantibodies bind the surface of apoptotic fetal cardiocytes and promote secretion of tumor necrosis factor a by macrophages . J Immunol 2000; 165: 5345–5351 .

13.

Garcia S , Nascimento JHM , Bonfa E , Levy R , Oliveira SF , Tavares AV , Campos deCarvalho AC . Cellular mechanism of the conduction abnormalities induced by serum from anti-Ro/SSA-positive patients in rabbit hearts . J Clin Invest 1994; 93: 718–724 .

14.

Boutjdir M , Chen L , Zhang Z , Tseng C , Di Donato F , Rashbaum W , Morris A , El-Sherif N , Buyon JP . Arrhythmogenicity of IgG and anti-52 kDa SSA/Ro affinity purified antibodies from mothers of children with congenital heart block . Circulation Res 1997; 80: 354–362 .

15.

Xiao GQ , Hu K , Boutjdir M . Direct inhibition of expressed cardiac L-and T-type calcium channels by IgG from mothers whose children have congenital heart block . Circulation 2001; 103: 1599–1604 .

16.

Qu Y , Xiao GQ , Chen L , Boutjdir M . Autoantibodies from mothers of children with congenital heart block downregulate cardiac L-type calcium channels . J Mol Cell Cardiol 2001; 33: 1153–1156 .

17.

Miranda-Carús ME , Boutjdir M , Tseng CE , Di Donato F , Chan EKL , Buyon JP . Induction of antibodies reactive with SSA/Ro-SSB/La and development of congenital heart block in a murine model . J Immunol 1998; 161: 5886–5892 .

18.

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: 1658–1666 .

19.

Saleeb S , Copel J , Friedman D , Buyon JP . Comparison of treatment with fluorinated glucocorticoids to natural history of autoantibodyassociated congenital heart block: retrospective review of the research registry for neonatal lupus . Arthritis Rheum 1999; 42: 2335–2345 .

20.

Glickstein JS , Buyon JP , Friedman D . The fetal PR interval: pulsed Doppler echocardiographic assessment . Am J Cardiol 2000; 86: 236–239 .

21.

Geggel RL , Tucker L , Szer I . Postnatal progression from second-to third-degree heart block in neonatal lupus syndrome . J Pediatr 1988; 113: 1049–1052 .

22.

Buyon JP . The role of anti-SSA/Ro-SSB/La autoantibodies in neonatal lupus. In: Kammer GM , Tsokos GC (eds). Lupus: cellular and molecular pathogenesis. Humana Press: Totowa, NJ , 1999, pp 492–514.

23.

Ho YS , Esscher E , Anderson RH , Michaelsson M . Anatomy of congenital complete heart block and relation to maternal anti-Ro antibodies . Am J Cardiol 1986; 58: 291–294 .

24.

Mazel JA , El-Sherif N , Buyon J , Boutjdir M . Electrocardiographic abnormalities in a murine model injected with IgG from mothers of children with congenital heart block . Circulation 1999; 99: 1914–1918 .