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Cardiac Autoantibodies from Patients Affected by a New Variant of Endemic Pemphigus Foliaceus in Colombia, South America

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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.

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Abbreviations

BMZ:

Basement membrane zone

EPF:

Endemic pemphigus foliaceus

El Bagre-EPF:

El Bagre endemic pemphigus foliaceus

ICS:

Intercellular staining between keratinocytes

IB:

Immunoblotting

DIF:

Direct immunofluorescence

IIF:

Indirect immunofluorescence

TTS:

Transverse tubule system

IEM:

Immunoelectron microscopy

H&E:

Hematoxylin and eosin

ARVC:

Arrhythmogenic right ventricular cardiomyopathy

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Funding Sources

This study was supported by Georgia Dermatopathology Associates, Atlanta, Georgia, USA (MSH). The El Bagre-EPF samples were collected through previous grants from the University of Antioquia, the Embassy of Japan in Colombia, the Mineros de Antioquia SA, DSSA, the Hospital Nuestra Senora del Carmen, all in Medellin, Colombia, South America (AMAV). H & E, IHC, DIF, IIF, and IEM studies were funded by Georgia Dermatopathology Associates (MSH and AMAV). Confocal studies were performed with funds from the Department of Ophthalmology, Emory University Medical Center, Atlanta, Georgia, USA (HG) (NIH NEI EY06360) and P01 HL058000 from (SCD).

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Author information

Authors and Affiliations

  1. Georgia Dermatopathology Associates, Atlanta, Georgia, USA

    Ana Maria Abreu-Velez & Michael S. Howard

  2. Department of Cardiology, Emory University Medical Center, Atlanta, Georgia, USA

    Zhe Jiao

  3. Department of Ophthalmology, Emory University Medical Center, Atlanta, Georgia, USA

    Weiqing Gao & Hans E. Grossniklaus

  4. Robert P. Apkarian Integrated Electron Microscopy Core, Emory University Medical Center, Atlanta, Georgia, USA

    Hong Yi

  5. Chief Cardiac Electrophysiology Las Americas Clinic, Chief Cardiology General Hospital of Medellin, and Chief Section of Cardiology, CES, Medellin, Colombia

    Mauricio Duque-Ramírez

  6. Chief Section of Cardiology, University of Illinois at Chicago (UIC) Medical Center, Chicago, USA

    Samuel C. Dudley Jr.

Authors
  1. Ana Maria Abreu-Velez
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  2. Michael S. Howard
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  3. Zhe Jiao
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  4. Weiqing Gao
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  5. Hong Yi
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  6. Hans E. Grossniklaus
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  7. Mauricio Duque-Ramírez
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  8. Samuel C. Dudley Jr.
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Corresponding author

Correspondence to Ana Maria Abreu-Velez.

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Abreu-Velez, A.M., Howard, M.S., Jiao, Z. et al. Cardiac Autoantibodies from Patients Affected by a New Variant of Endemic Pemphigus Foliaceus in Colombia, South America. J Clin Immunol 31, 985–997 (2011). https://doi.org/10.1007/s10875-011-9574-y

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  • DOI: https://doi.org/10.1007/s10875-011-9574-y

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