Neonatal molecular pathologies induced by maternal anti-Ro and anti-La antibodies

Authors

  • Rafael Herrera-Esparza Laboratorios de Inmunología y Biología Molecular, UA Ciencias Biológicas, Universidad Autónoma de Zacatecas. 98040 Zacatecas, ZAC.
  • Esperanza Avalos-Díaz Laboratorios de Inmunología y Biología Molecular, UA Ciencias Biológicas, Universidad Autónoma de Zacatecas. 98040 Zacatecas, ZAC.

DOI:

https://doi.org/10.15305/ijrci/v3i1/150

Keywords:

Congenital heart block, Anti-Ro antibodies, Anti-La antibodies, Calcium channels

Abstract

Maternal antinuclear antibodies with anti-Ro or anti-La specificity might be pathogenic to the fetus and could induce molecular neonatal pathologies, such as neonatal lupus (NL) with or without congenital heart block (CHB).  The cutaneous manifestations of neonatal lupus appear at birth or a few weeks later, and skin lesions may persist for weeks. While CHB is characterized by intrauterine bradycardia or low heart rates at birth and may persist for months, depending on the degree of blockage. Clinical and experimental data demonstrated that anti-Ro and anti-La autoantibodies functionally inhibit L-type calcium channels and induce abnormalities in electrical conduction of the cardiac myocytes. It has been 38 years since the first clinical description of CHB. Presently, the pathophysiology of CHB has been clarified through clinical and basic research studies.

Author Biographies

Rafael Herrera-Esparza, Laboratorios de Inmunología y Biología Molecular, UA Ciencias Biológicas, Universidad Autónoma de Zacatecas. 98040 Zacatecas, ZAC.

Chief of the Laboratorios de Inmunologia y Biologia Molecular

Esperanza Avalos-Díaz, Laboratorios de Inmunología y Biología Molecular, UA Ciencias Biológicas, Universidad Autónoma de Zacatecas. 98040 Zacatecas, ZAC.

Laboratorios de Inmunología y Biología Molecular

References

Wolin S. RNPs and autoimmunity: 20 years later. RNA. 2015; 21(4):248-49.

Chen X, Taylor DW, Galan JE, Wang HW, Wolin SL. An RNA degradation machine sculpted by Ro autoantigen and noncoding RNA. Cell. 2013; 153(1):166-77.

Wolin SL, Belair C, Bocciotto M, Chen X, Taylor DW, Wang HW. Non-coding Y RNAs as tethers and gates. Insights from bacteria. RNA Biology. 2013; 10(10):1602-1608.

O´Brien CA, Wolin SL. A possible role for the 60-kD Ro autoantigen in a discard pathway for defective 5S rRNA precursors. Genes Dev. 1994; 8(23):2891-903.

Campos-Almaraz ML, Fraire-Velázquez S, Moreno J, Herrera-Esparza R. The 5S rRNA is associated with Ro60 ribonucleoprotein and is co-precipitated with hYRNAs by anti-Ro antibodies. Autoimmunity. 1999; 31(2):95-101.

Köhn M, Pazaitis N, Hüttelmaier S. Why Y RNAs? About versatile RNAs and their functions. Biomolecules. 2013; 3(1):143-56.

Espinosa A, Zhou W, Ek M, Hedlund M, Brauner S, Popovic K, et al. The Sjögren syndrome associated autoantigen Ro52 is an E3 ligase that regulate proliferation and cell death. J Immunol. 2006; 176(10):6277-85.

Kong HJ, Anderson DE, Lee CH, Jand MK, Tamura T, Tailor P, et al. Cutting edge: Autoantigen Ro52 is an interferon inducible E3 ligase that ubiquitinates IRF-8 and enhances cytokine expression in macrophages. J Immunol. 2007; 179(1):26-30.

Chasapis C, Argyriou AI, Apositolidi M, Konstantinidou P, Bentrop D, Stathopoulos C, et al. 1H,13C and 15N backbone and side chain ressonance assignment of the LAM-RRM1 N-terminal module of La protein from Dictyostelium discoideum. Biomol NMR assign, 2015; DOI 10.1007/s12104-015-9597-z

Liang C, Xiong K, Szulwach KE, Zhang Y, Wang Z, Peng J, et al. Sjögren syndrome antigen B (SSB)/La promotes global microRNA expression by binding microRNA precursors through stem-loop recognition. J Biol Chem. 2013; 288(1);723-36.

Peene I, Meheus L, Veys EM, De Keyser F. Diagnostic associations in a large and consecutively identified population positive for anti-SSA and/or anti-SSB: the range of associated diseases differs according to the detailed serotype. Ann Rheum Dis. 2002; 61(12):1090-4.

Yoshimi R, Ueda A, Ozato K, Ishigatsubo Y. Clinical and pathological roles of Ro/SSA autoantibody system. Clin Develop Immunol. 2012; 2012:606195.

To CH, Petri M. Is antibody clustering predictive of clinical subsets and damage in systemic lupus erythematosus. Arthritis Rheum 2005; 52(12);4003-10.

Provost TT, Herrera-Esparza R, Diaz LA. Nucleoprotein autoantibodies in lupus erythematosus, J Invest Dermatol 1985; 85(1 Suppl):133s-9s.

Biazar C, Sigges J, Patsinakidis N, Ruland V, Amler S, Bonsmann G, et al. Cutaneous lupus erythematosus: first multicenter database analysis of 1002 patients from the European Society of Cutaneous Lupus Erythematosus (EUSCLE). Autoimmune rev 2013; 12(3):444-54.

Popovic K, Brauner S, Ek M, Wahren-Herlenius M, Nyberg F. Fine specificity of the Ro/SSA autoantibody response in relation to serological and clinical findings in 96 patients with self-reported cutaneous symptoms induced by the sun. Lupus 2007; 16(1):10-7.

Chameides L, Truex RC, Vetter V, Rashkind WJ, Galioto FM Jr, Noonan JA. Association of maternal systemic lupus erythematosus with congenital complete heart block. N Engl J Med 1977; 297(22):1204-7.

Schmidt KG, Ulmer HE, Silverman NH, Kleinman CS, Copel JA. Perinatal outcome of fetal complete atrioventricular block: a multicenter experience. J Am Coll Cardiol. 1991; 17(6):1360-6.

Julkunen H, Kurki P, Kaaja R, Heikkila R, Immonen I, Chan EK, et al. Isolated congenital heart block. Long-term outcome of mothers and characterization of the immune response to SS-A/Ro and to SS-B/La. Arthritis Rheum. 1993; 36(11):1588-98.

Waltuck J, Buyon JP. Autoantibody-associated congenital heart block: outcome in mothers and children. Ann Intern Med. 1994; 120(7):544-551.

Silverman ED. Congenital heart block and neonatal lupus erythematosus: prevention is the goal. J Rheumatol. 1993; 20(7):1101-4.

Buyon JP, Hiebert R, Copel J, Craft J, Friedman D, Katholi M, et al. Autoimmune-associated congenital heart block: demographics, mortality, morbidity and recurrence rates obtained from a national neonatal lupus registry. J Am Coll Cardiol. 1998; 31(7):1658-66.

Brucato A, Cimaz R, Stramba-Badiale M. Neonatal lupus. Clin Rev Allergy Immunol. 2002; 23(3):279-99.

Capone C, Buyon JP, Friedman DM, Frishman WH. Cardiac manifestations of neonatal lupus: A review of autoantibody associated congenital heart block and its impact in an adult population. Cardiol Rev. 2012; 20(2):72-6.

Lee LA, Weston WL, Krueger GG, et al. An animal model of antibody binding in cutaneous lupus. Arthritis Rheum. 1986; 29(6):782-8.

Herrera-Esparza R, Villalobos R, Bollain-Y-Goytia JJ, Ramírez-Sandoval R, Sánchez-Rodriguez SH, Pacheco-Tovar G, et al. Apoptosis and redistribution of the Ro autoantigen in Balb/c mouse like in sub-acute cutaneous lupus erythematosus. Clin Dev Immunol. 2006; 13(2-4):163-6.

Buyon JP, Waltuck J, Caldwell K, Crawford B, Slade SG, Copel J, et al. Relationship between maternal and neonatal levels of antibodies to 48 kDa SSB(La), 52 kDa SSA(Ro), and 60 kDa SSA(Ro) in pregnancies complicated by congenital heart block. J Rheumatol. 1994; 21(10):1943-50.

Buyon JP, Waltuck J, Kleinman C, Copel J. In utero identification and therapy of congenital heart block. Lupus. 1995; 4(2):116-21.

Tseng CE, Caldwell K, Feit S, Chan EK, Buyon JP. Subclass distribution of maternal and neonatal anti-Ro(SSA) and La(SSB) antibodies in congenital heart block. J Rheumatol. 1996; 23(5):925-32.

Boutjdir M, Chen L, Zhang ZH, Tseng CE, DiDonato F, Rashbaum W, et al. Arrhythmogenicity of IgG and anti-52-kD SSA/Ro affinity-purified antibodies from mothers of children with congenital heart block. Circ Res. 1997; 80(3):354-62.

Friedman DM, Rupel A, Glickstein J, Buyon JP. Congenital heart block in neonatal lupus: the pediatric cardiologist’s perspective. Indian J Pediatr. 2002; 69(6):517-22.

Buyon JP, Tseng CE, Di Donato F, Rashbaum W, Morris A, Chan EK. Cardiac expression of 52beta, an alternative transcript of the congenital heart block-associated 52-kd SS-A/Ro autoantigen, is maximal during fetal development. Arthritis Rheum. 1997; 40(4):655-60.

Boutjdir M, Chen L, Zhang ZH, Tseng CE, El-Sherif N, Buyon JP. Serum and immunoglobulin G from the mother of a child with congenital heart block induce conduction abnormalities and inhibit L-type calcium channels in a rat heart model. Pediatr Res. 1998; 44(1):11-9.

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 (14):1914-8.

Restivo M, Kozhevnikov DO, Boutjdir M. Optical mapping of activation patterns in an animal model of congenital heart block. Am J Physiol Heart Circ Physiol. 2001; 280(4):H1889-95.

Garcia S, Nascimento JH, Bonfa E, Levy R, Oliveira SF, Tavares AV, de Carvalho AC. Cellular mechanism of the conduction abnormalities induced by serum from anti-Ro/SSA-positive patients in rabbit hearts. J Clin Invest. 1994; 93(2):718-24.

Miranda-Carús ME, Boutjdir M, Tseng CE, Di-Donato F, Chan EK, 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(11):5886-92.

Hamilton RM, Lee-Poy M, Kruger K, Silverman ED. Investigative methods of congenital heart block. J Electrocardiol. 1998; 30 Suppl:69-74.

Viana VS, Garcia S, Nascimento JH, Elkon KB, Brot N, Campos de Carvalho AC, et al. Induction of in vitro heart block is not restricted to affinity purified anti-52 kDa Ro/SSA antibody from mothers of children with neonatal lupus. Lupus. 1998; 7(3):141-7.

Boutjdir M. Molecular and ionic basis of congenital complete heart block. Trends Cardiovasc Med. 2000; 10(3):114-22.

Qu Y, Boutjdir M. Pathophysiology of autoimmune-associated congenital heart block. Applied Cardiopulmonary Pathophysiology. 2012; 16:96-112.

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(1):11-7.

Qu Y, Baroudi G, Yue Y, Boutjdir M. Novel molecular mechanism involving alpha1D (Cav1.3) L-type calcium channel in autoimmune-associated sinus bradycardia. Circulation. 2005; 111(23):3034-41.

Gardiner HM, Belmar C, Pasquini L, Seale A, Thomas M, Dennes W, et al. Fetal ECG: a novel predictor of atrioventricular block in anti-Ro positive pregnancies. Heart. 2007; 93(11):1454-60.

Buyon JP, Clancy RM, Friedman DM. Autoimmune associated congenital heart block: integration of clinical and research clues in the management of the maternal / foetal dyad at risk. J Intern Med. 2009; 265(6):653-62.

Ambrosi A, Dzikaite V, Park J, Strandberg L, Kuchroo VK, Herlenius E, et al. Anti-Ro52 monoclonal antibodies specific for amino acid 200-239, but not other Ro52 epitopes, induce congenital heart block in a rat model. Ann Rheum Dis. 2012; 71(3):448-54.

Shaw RM, Colecraft HM. L-type calcium channel targeting and local signaling in cardiac myocytes. Cardiovasc Res. 2013; 98(2):177-86.

Tang ZZ, Liang MC, Lu S, Yu D, Yu CY, Yue DT, et al. Transcript scanning reveals novel and extensive splice variations in human l-type voltage-gated calcium channel, Cav1.2 alpha1 subunit. J Biol Chem. 2004; 279(43):44 335-43.

Hofmann F, Flockerzi V, Kahl S, Wegener JW. L-type CaV1.2 calcium channels: from in vitro findings to in vivo function. Physiol Rev. 2014; 94(1):303-26.

Brucato A, Cimaz R, Catelli L, Meroni P. Anti-Ro-associated sinus bradycardia in newborns. Circulation. 2000; 102 (11): E88-9.

Hu K, Qu Y, Yue Y, Boutjdir M. Functional basis of sinus bradycardia in congenital heart block. Circ Res. 2004; 94(4):e32-8.

Miranda-Carús ME, Askanase AD, Clancy RM, Di Donato F, Chou TM, Libera MR, et al. Anti-SSA/Ro and anti-SSB/La autoantibodies bind the surface of apoptotic fetal cardiocytes and promote secretion of TNF-alpha by macrophages. J Immunol. 2000; 165(9):5345-51.

Clancy RM, Askanase AD, Kapur RP, Chiopelas E, Azar N, Miranda-Carus ME, et al. Trans differentiation of cardiac fibroblasts, a fetal factor in anti-SSA/Ro-SSB/La antibody-mediated congenital heart block. J Immunol. 2002; 169(4):2156-63.

Karnabi E, Qu Y, Wadgaonkar R, Mancarella S, Yue Y, Chahine M, et al. Congenital heart block: identification of autoantibody binding site on the extracellular loop (domain I, S5-S6) of alpha(1D) L-type Ca channel. J Autoimmun. 2010; 34(2):80-86.

Strandberg LS, Cui X, Rath A, Liu J, Silverman ED, Liu X, et al. Congenital heart block maternal sera autoantibodies target an extracellular epitope on the α1G T-type calcium channel in human fetal hearts. PLoS One. 2013; 8(9):e72668.

Downloads

Additional Files

Published

19-08-2015

Issue

Section

Reviews