Abstract
Few diseases exemplify the integration of research from bench to bedside as well as neonatal lupus, often referred to as a model of passively acquired autoimmunity. In essence, this disease encompasses two patients, both the mother and her child. The signature histologic lesion of autoimmune-associated congenital heart block is fibrosis of the conducting tissue, and in some cases the surrounding myocardium. It is astounding how rapid and, in most cases, irreversible is the fibrotic response to injury. The mechanism by which maternal anti-SSA/Ro-SSB/La antibodies initiate and perpetuate inflammation, and eventuate in scarring of the atrioventricular node, is not yet defined. In vitro and in vivo studies suggest that one pathologic cascade leading to scarring may be initiated via apoptosis, resulting in translocation of SSA/Ro-SSB/La antigens and subsequent surface binding by maternal autoantibodies. These opsonized cardiocytes are phagocytosed by macrophages, which secrete factors that transdifferentiate fibroblasts into myofibroblasts, a scarring phenotype. Dissecting the individual components in this fibrotic pathway should provide insights into the rarity of irreversible injury and should form the basis of rational approaches to prevention and treatment.
Publication types
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Editorial
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adult
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Antibodies, Antinuclear / immunology
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Atrioventricular Node / embryology
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Atrioventricular Node / immunology
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Atrioventricular Node / pathology*
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Autoantigens*
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Autoimmune Diseases / complications
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Autoimmune Diseases / congenital*
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Autoimmune Diseases / embryology
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Autoimmune Diseases / immunology
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Autoimmune Diseases / pathology
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Female
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Fetal Heart / immunology
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Fetal Heart / pathology
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Fibroblasts / pathology
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Fibrosis
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Heart Block / congenital*
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Heart Block / etiology
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Heart Block / immunology
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Heart Block / pathology
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Humans
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Immunity, Maternally-Acquired*
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Infant, Newborn
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Inflammation
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Isoantibodies / immunology
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Isoantibodies / metabolism
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Lupus Erythematosus, Systemic / complications
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Lupus Erythematosus, Systemic / congenital*
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Lupus Erythematosus, Systemic / embryology
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Lupus Erythematosus, Systemic / immunology
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Lupus Erythematosus, Systemic / pathology
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Macrophages / pathology
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Myocytes, Cardiac / immunology
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Myocytes, Cardiac / pathology
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Pregnancy
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RNA, Small Cytoplasmic*
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Ribonucleoproteins / immunology
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SS-B Antigen
Substances
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Antibodies, Antinuclear
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Autoantigens
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Isoantibodies
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RNA, Small Cytoplasmic
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RO60 protein, human
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Ribonucleoproteins
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SS-A antibodies
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SS-A antigen
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SS-B antibodies