title: Cardiac autoantibodies from patients affected by a new variant of endemic pemphigus foliaceus in Colombia, South America.
abstract: Several patients affected by a new variant of endemic pemphigus foliaceus in El Bagre, Colombia (El Bagre-EPF) have experienced a sudden death syndrome, including persons below the age of 50. El Bagre-EPF patients share several autoantigens with paraneoplastic pemphigus patients, such as reactivity to plakins. Further, paraneoplastic pemphigus patients have autoantibodies to the heart. Therefore, we tested 15 El Bagre-EPF patients and 15 controls from the endemic area for autoreactivity to heart tissue using direct and indirect immunofluorescence, confocal microscopy, immunohistochemistry, immunoblotting, and immunoelectron microscopy utilizing heart extracts as antigens. We found that 7 of 15 El Bagre patients exhibited a polyclonal immune response to several cell junctions of the heart, often colocalizing with known markers. These colocalizing markers included those for the area composita of the heart, such as anti-desmoplakins I and II; markers for gap junctions, such as connexin 43; markers for tight junctions, such as ezrin and junctional adhesion molecule A; and adherens junctions, such pan-cadherin. We also detected colocalization of the patient antibodies within blood vessels, Purkinje fibers, and cardiac sarcomeres. We conclude that El Bagre-EPF patients display autoreactivity to multiple cardiac epitopes, that this disease may resemble what is found in patients with rheumatic carditis, and further, that the cardiac pathophysiology of this disorder warrants further evaluation.
authors.affiliation: Georgia Dermatopathology Associates, Atlanta, Georgia, USA. abreuvelez@yahoo.com
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Abreu-Velez
authors.forename: Michael S
authors.initials: MS
authors.lastname: Howard
authors.forename: Zhe
authors.initials: Z
authors.lastname: Jiao
authors.forename: Weiqing
authors.initials: W
authors.lastname: Gao
authors.forename: Hong
authors.initials: H
authors.lastname: Yi
authors.forename: Hans E
authors.initials: HE
authors.lastname: Grossniklaus
authors.forename: Mauricio
authors.initials: M
authors.lastname: Duque-Ramírez
authors.forename: Samuel C
authors.initials: SC
authors.lastname: Dudley
mesh_terms: D000328:Adult; D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism; D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism*; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism; D015820:Cadherins / Q000276:immunology / Q000378:metabolism; D002417:Cattle; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism; D003105:Colombia; D018031:Connexin 43 / Q000276:immunology / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000276:immunology / Q000378:metabolism; D016757:Death, Sudden, Cardiac; D051180:Desmoplakins / Q000276:immunology / Q000378:metabolism; D019353:Endemic Diseases; D006321:Heart / Q000502:physiology / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D007365:Intercellular Junctions / Q000648:ultrastructure; D051379:Mice; D008854:Microscopy, Electron; D008875:Middle Aged; D009206:Myocardium / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D010392:Pemphigus / Q000453:epidemiology* / Q000276:immunology* / Q000401:mortality / Q000503:physiopathology; D051381:Rats; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism; D055815:Young Adult; D000099149:Ezrin
chemical_list: D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D001324:Autoantigens; D015820:Cadherins; D015815:Cell Adhesion Molecules; D018031:Connexin 43; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; D011956:Receptors, Cell Surface; D000099149:Ezrin; C407243:F11R protein, human