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.

Autoimmunoreactive IgGs against cardiac lipid raft-associated proteins in patients with postural orthostatic tachycardia syndrome

“…Many of the proteins have previously been implicated in cardiac dysfunction or cardiac disease, such as S100A8 20 , HSP70 21 , desmin 22 , and desmoplakin 23 . However, involvement of these proteins in the pathogenesis of POTS is unknown.…”

Dermatitis herpetiformis bodies and autoantibodies to noncutaneous organs and mitochondria in dermatitis herpetiformis

“…For colocalization experiments with the dermatitis herpetiformis serum autoantibodies, we used antibodies to desmoplakins 1 and 2, (DI-DPII), armadillo repeat gene deleted in velocardiofacial syndrome (ARVCF) and anti-p0071 (Progen Biotechnik, Heidelberg, Germany). Our studies were performed as previously described [7][8][9][10][11][12][13].…”

“…As experimental controls, we utilized 1) an anti-desmoplakin multiepitope cocktail from Progen (Heidelberg, Germany), 2) the serum of a patient with bullous pemphigoid that recognized bullous pemphigoid antigens 1 and 2 (230 and 180 kDa, respectively), and 3) serum from a patient with paraneoplastic pemphigus. Our IB was performed as previously described [7][8][9][10][11][12][13].…”

“…Positive and negative controls were consistently performed. Our studies were specifically performed as previously described [7][8][9][10][11][12][13].…”

“…Our technique was performed as previously described [7][8][9][10][11][12][13]. In brief, postembedding immunogold labeling was performed on samples of El Bagre-EPF sera and controls.…”