Autoimmune-associated congenital heart block: dissecting the cascade from immunologic insult to relentless fibrosis

The Anatomical Record. Part A, Discoveries in Molecular, Cellular, and Evolutionary Biology
Robert Clancy, Jill P Buyon

Abstract

Few diseases exemplify the integration of research from bench to bedside as well as neonatal lupus, often described as a model of passively acquired autoimmunity. The signature histologic lesion of autoimmune congenital heart block (CHB) is fibrosis of the conducting tissue and, in some cases, the surrounding myocardium. Although anti-SSA/Ro-SSB/La antibodies are detected in > 85% of mothers whose fetuses are identified with conduction abnormalities in a structurally normal heart, the risk for a woman with the candidate antibodies to have a child with CHB is 2%. The mechanism by which maternal anti-SSA/Ro-SSB/La antibodies initiate and finally eventuate in atrioventricular nodal scarring is not yet defined, but it is clear that the antibodies alone are insufficient to cause disease and fetal factors are likely contributory. Previous in vitro and in vivo studies suggest that the pathologic cascade is initiated via apoptosis, resulting in translocation of SSA/Ro-SSB/La antigens to the cell surface where they are bound by maternal autoantibodies. Subsequently, the Fc portion of the bound immunoglobulin engages Fcgamma receptors on tissue macrophages, resulting in release of TGF-beta at a threshold favoring a profibrotic milieu and...Continue Reading

Associated Clinical Trials

References

Dec 1, 1977·The New England Journal of Medicine·L ChameidesJ A Noonan
Jan 1, 1992·Experimental Lung Research·S H Phan, S L Kunkel
Jan 1, 1991·The Journal of Clinical Investigation·E K ChanE M Tan
Feb 1, 1990·The Journal of Pediatrics·R M LaxerE D Silverman
May 1, 1990·Arthritis and Rheumatism·J P Buyon, R Winchester
Aug 1, 1989·Journal of Autoimmunity·J B Harley
Dec 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·S L DeutscherJ D Keene
Dec 1, 1988·British Heart Journal·M V MachadoL D Allan
May 1, 1988·The Journal of Experimental Medicine·E Ben-ChetritE M Tan
Jul 1, 1985·Clinical Immunology and Immunopathology·M J FritzlerT J Bowen
Feb 1, 1984·Arthritis and Rheumatism·C E HarmonE M Tan
Jul 28, 1983·The New England Journal of Medicine·J S ScottR P Skinner
Sep 1, 1981·The Journal of Investigative Dermatology·D C KephartT T Provost
Jun 1, 1995·Clinical and Experimental Immunology·E D SilvermanK B Elkon
Jun 1, 1994·The Journal of Investigative Dermatology·L A LeeM Reichlin
Jan 1, 1996·Molecular Biology Reports·D WangE K Chan
Dec 6, 1997·Nature·R E VollI Girkontaite
Jul 8, 1999·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·A El-GamelI V Hutchinson
Oct 25, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·M E Miranda-CarúsJ P Buyon
Jan 12, 2001·Journal of the American College of Cardiology·J P MoakJ P Buyon

❮ Previous
Next ❯

Citations

Oct 11, 2005·Autoimmunity Reviews·Patrizia Rovere-QueriniMaria Grazia Sabbadini
Aug 30, 2008·Clinical and Experimental Immunology·L StrandbergM Wahren-Herlenius
Sep 29, 2012·The Journal of Pathology·Domenico Del PrincipeAnna Maria Giammarioli
Aug 6, 2013·Pediatrics International : Official Journal of the Japan Pediatric Society·Tetsuya IsayamaHiroyuki Kitajima
Dec 3, 2014·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Pietro Enea LazzeriniFranco Laghi-Pasini
Oct 19, 2006·Journal of the American College of Cardiology·Elisabeth VillainDamien Bonnet
Aug 27, 2021·Frontiers in Cardiovascular Medicine·Kavya L SingampalliKathryn Jane Grande-Allen

❮ Previous
Next ❯

Related Concepts

Related Feeds

Birth Defects

Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis