Chinese Medical E-ournals Database

Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition) ›› 2019, Vol. 15 ›› Issue (05): 486 -491. doi: 10.3877/cma.j.issn.1673-5250.2019.05.002

Special Issue:

Special Forum

Etiology and pathogenic mechanism of neonatal lupus syndromes: a comprehensive review

Lei Liu1, Yi Zhang1, Kaiyu Zhou1,()   

  1. 1. Department of Pediatric Cardiovascular, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Key Laboratory of Development and Related Diseases of Women and Children of Sichuan Province, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
  • Received:2018-04-25 Revised:2018-10-16 Published:2019-10-01
  • Corresponding author: Kaiyu Zhou
  • About author:
    Corresponding author: Zhou Kaiyu, Email:
  • Supported by:
    National Natural Science Foundation of China(81570369, 81571515); Program for Changjiang Scholars and Innovative Research Team in University(IRT0935); Science and Technology Program for the Wellbeing of Chengdu Science and Technology Bureau(2015-HM01-00456-SF)

Neonatal lupus syndromes (NLS) is an acquired autoimmune disease, which is mediated by maternal antibodies. Maternal anti-Sjogren′s syndrome A (SSA)/Ro, and anti-Sjogren′s syndrome B (SSB)/La antibodies are related with the transient cutaneous lupus and (or) transient/permanent congenital heart block (CHB). Though NLS is rare, it is seriously harmful to children or fetuses with CHB. There are many studies on the etiology and pathogenic mechanism of NLS, but the specific factors leading to the occurrence and development of NLS are still unclear. This article focuses on the current researches on etiology and pathogenesis of NLS and provides references for clinical treatment and further research of NLS.

图1 胎儿自身抗SSA/Ro与抗SSB/La抗体介导的胎儿AVB发生机制的3个时期示意图
[1]
Vanoni F, Lava SAG, Fossali EF, et al. Neonatal systemic lupus erythematosus syndrome: a comprehensive review[J]. Clin Rev Allerg Immu, 2017, 53(3): 469-476.
[2]
Zuppa AA, Riccardi R, Frezza S, et al. Neonatal lupus: follow-up in infants with anti-SSA/Ro antibodies and review of the literature[J]. Autoimmun Rev, 2017, 16(4): 427-432.
[3]
Chang C. The pathogenesis of neonatal autoimmune and autoinflammatory diseases: a comprehensive review[J]. J Autoimmun, 2013, 41: 100-110.
[4]
Hasbún T, Chamlin SL. A 6-week-old boy with annular skin lesions. Neonatal lupus erythematosus[J]. Pediatr Ann, 2014, 43(1): e1-e3.
[5]
Ambrosi A, Wahren-Herlenius M. Congenital heart block: evidence for a pathogenic role of maternal autoantibodies[J]. Arthritis Res Ther, 2012, 14(2): 208.
[6]
Brito-Zerón P, Izmirly PM, Ramoscasals M, et al. The clinical spectrum of autoimmune congenital heart block[J]. Nat Rev Rheumatol, 2015, 11(5): 301-312.
[7]
Donofrio MT, Moon-Grady AJ, Hornberger LK, et al. Diagnosis and treatment of fetal cardiac disease: a scientific statement from the American Heart Association[J]. Circulation, 2014, 129(21): 2183-2242.
[8]
Brooks P. Fetal manifestations of maternal anti-Ro and La antibodies - more than complete heart block[J]. Australas J Ultrasound Med, 2015, 18(3): 124-128.
[9]
Saxena A, Izmirly PM, Mendez B, et al. Prevention and treatment in utero of autoimmune-associated congenital heart block[J]. Cardiol Rev, 2014, 22(6): 263-267.
[10]
Chandler SF, Fynn-Thompson F, Mah DY. Role of cardiac pacing in congenital complete heart block[J]. Expert Rev Cardiovasc Ther, 2017, 15(11): 853-861.
[11]
Brito-Zerón P, Izmirly PM, Ramos-Casals M, et al. Autoimmune congenital heart block: complex and unusual situations[J]. Lupus, 2016, 25(2): 116-128.
[12]
Chang C. Neonatal autoimmune diseases: a critical review[J]. J Autoimmun, 2012, 38(2-3): J223-J238.
[13]
Zhou KY, Hua YM. Autoimmune-associated congenital heart block: a new insight in fetal life[J]. Chin Med J, 2017, 130(23): 2863-2871.
[14]
Ambrosi A, Sonesson SE, Wahren-Herlenius M. Molecular mechanisms of congenital heart block[J]. Exp Cell Res, 2014, 325(1): 2-9.
[15]
Fayyaz A, Kurien BT, Scofield RH. Autoantibodies in Sjögren′s syndrome[J]. Rheum Dis Clin North Am, 2016, 42(3): 419-434.
[16]
Nahal SK, Selmi C, Gershwin ME. Safety issues and recommendations for successful pregnancy outcome in systemic lupus erythematosus[J]. J Autoimmunity, 2018, 93: 16-23.
[17]
Izmirly P, Saxena A, Buyon JP. Progress in the pathogenesis and treatment of cardiac manifestations of neonatal lupus[J]. Curr Opin Rheumatol, 2017, 29(5): 467-472.
[18]
Ambrosi A, Dzikaite V, Park J, 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[J]. Ann Rheum Dis, 2012, 71(3): 448-454.
[19]
Reed JH, Clancy RM, Lee KH, et al. Umbilical cord blood levels of maternal antibodies reactive with p200 and full-length Ro 52 in the assessment of risk for cardiac manifestations of neonatal lupus[J]. Arthritis Care Res (Hoboken), 2012, 64(9): 1373-1381.
[20]
Anami A, Fukushima K, Takasaki Y, et al. The predictive value of anti-SS-A antibodies titration in pregnant women with fetal congenital heart block[J]. Mod Rheumatol, 2013, 23(4): 653-658.
[21]
Tunks RD, Clowse ME, Miller SG, et al. Maternal autoantibody levels in congenital heart block and potential prophylaxis with antiinflammatory agents[J]. Am J Obstet Gynecol, 2013, 208(1): 61-64.
[22]
Tonello M, Hoxha A, Mattia E, et al. Low titer, isolated anti Ro/SSA 60 kd antibodies is correlated with positive pregnancy outcomes in women at risk of congenital heart block[J]. Clin Rheumatol, 2017, 36(5): 1155-1160.
[23]
Tonello M, Ruffatti A, Favaro M, et al. Maternal autoantibody profiles at risk for autoimmune congenital heart block: a prospective study in high-risk patients[J]. Lupus Sci Med, 2016, 3(1): e000129.
[24]
Hunter LE, Simpson JM. Atrioventricular block during fetal life[J]. J Saudi Heart Assoc, 2015, 27(3): 164-178.
[25]
Madhusudan D, Raju A, Vijaya N. Correlation of maternal autoantibodies with fetal congenital heart block[J]. J Obstet Gynaecol India, 2016, 66(Suppl 1): 112-116.
[26]
Meisgen S, Östberg T, Salomonsson S, et al. The HLA locus contains novel foetal susceptibility alleles for congenital heart block with significant paternal influence[J]. J Intern Med, 2014, 275(6): 640-651.
[27]
Tang L, Chen B, Ma B, et al. Association between IRF5 polymorphisms and autoimmune diseases: a Meta-analysis[J]. Genet Mol Res, 2014, 13(2): 4473-4485.
[28]
Lisney AR, Szelinski F, Reiter K, et al. High maternal expression of SIGLEC1 on monocytes as a surrogate marker of a type Ⅰ interferon signature is a risk factor for the development of autoimmune congenital heart block[J]. Ann Rheum Dis, 2017, 76(8): 1476-1480.
[29]
张艺凡,牛广华,赵高阳,等. 新生儿狼疮病的研究进展[J]. 临床儿科杂志,2013, 31(10): 994-997.
[30]
Meisgen S, Tingström J, Skog Andreasson A, et al. Environmental and lifestyle factors influencing risk of congenital heart block during pregnancy in anti-Ro/SSA-positive women[J]. RMD Open, 2017, 3(2): e000520.
[31]
Huang YH, Li SC, Huang LH, et al. Identifying genetic hypomethylation and upregulation of Toll-like receptors in Kawasaki disease[J]. Oncotarget, 2017, 8(7): 11249-11258.
[32]
Reed JH, Sim S, Wolin SL, et al. Ro60 requires Y3 RNA for cell surface exposure and inflammation associated with cardiac manifestations of neonatal lupus[J]. J Immunol, 2013, 191(1): 110-116.
[33]
Clancy RM, Markham AJ, Buyon JP. Endosomal Toll-like receptors in clinically overt and silent autoimmunity[J]. Immunol Rev, 2016, 269(1): 76-84.
[34]
Singh AG, Chowdhary VR. Pregnancy-related issues in women with systemic lupus erythematosus[J]. Int J Rheum Dis, 2015, 18(2): 172-181.
[35]
Leroux M, Desveaux C, Parcevaux M, et al. Impact of hydroxychloroquine on preterm delivery and intrauterine growth restriction in pregnant women with systemic lupus erythematosus: a descriptive cohort study[J]. Lupus, 2015, 24(13): 1384-1391.
[36]
Karnabi E, Qu Y, Mancarella S, et al. Rescue and worsening of congenital heart block-associated electrocardiographic abnormalities in two transgenic mice[J]. J Cardiovasc Electrophysiol, 2011, 22(8): 922-930.
[37]
Strandberg LS, Cui X, Rath A, et al. Congenital heart block maternal sera autoantibodies target an extracellular epitope on the α1G T-type calcium channel in human fetal hearts[J]. PLoS One, 2013, 8(9): e72668.
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