Neonatal lupus: advances in understanding pathogenesis and identifying treatments of cardiac disease

Curr Opin Rheumatol. 2012 Sep;24(5):466-72. doi: 10.1097/BOR.0b013e328356226b.

Abstract

Purpose of review: Cardiac manifestations of neonatal lupus include anti-SSA/Ro-SSB/La-mediated conduction system disease and endocardial/myocardial damage resulting in cardiomyopathy. This review will focus on recent data regarding updates on the proposed pathogenesis of disease, morbidity and mortality, and preventive and treatment therapies.

Recent findings: Evidence from animal models suggests that reactivity to the p200 region of the Ro52 protein, as well as antibody targeting of L-type calcium channels may be important in the development of cardiac neonatal lupus. In-vitro studies support a protective role of β-2 glycoprotein 1 (prevents anti-Ro binding to apoptotic cells) and pathologic roles of the urokinase-plasminogen activator/receptor system (leads to activation of TGF-β), and endothelin-1 secretion by macrophages in mediating tissue injury. Genetic studies highlight the fetal major histocompatibility complex in the development of disease, and a multigenerational study demonstrates that mothers of neonatal lupus children accumulate genetic risk factors preferentially from the neonatal lupus child's grandparents. Retrospective studies identify demographic and echocardiographic risk factors for morbidity and mortality and address the role of fluorinated steroids, intravenous immunoglobulin and hydroxychloroquine for prevention and treatment of disease.

Summary: Animal studies, in-vitro experiments, genetic analysis and clinical-translational research in cardiac neonatal lupus reveal novel insights and targets for therapy in this often devastating disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cardiomyopathies / congenital
  • Cardiomyopathies / etiology
  • Cardiomyopathies / immunology
  • Cardiomyopathies / therapy
  • Disease Models, Animal
  • Genome-Wide Association Study
  • Heart Block / congenital
  • Heart Block / etiology
  • Heart Block / immunology
  • Heart Block / therapy
  • Heart Diseases / congenital*
  • Heart Diseases / etiology
  • Heart Diseases / immunology
  • Heart Diseases / therapy
  • Humans
  • Infant, Newborn
  • Lupus Erythematosus, Systemic / congenital*
  • Lupus Erythematosus, Systemic / etiology
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Erythematosus, Systemic / therapy
  • Polymorphism, Single Nucleotide
  • Ribonucleoproteins / immunology

Substances

  • Ribonucleoproteins
  • SS-A antigen

Supplementary concepts

  • Neonatal Systemic lupus erythematosus