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Neural System Antigens Are Recognized by Autoantibodies from Patients Affected by a New Variant of Endemic Pemphigus Foliaceus in Colombia

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Abstract

Background

Endemic pemphigus foliaceus (EPF), is also known as “fogo selvagem” or “wild fire,” reflecting the intense burning sensation of the skin reported by patients with this disease. Based on this finding, we tested for neural autoreactivity in patients affected by a new variant of EPF (El Bagre-EPF).

Methods

We tested 20 El Bagre-EPF patients, 20 normal controls from the endemic area, and 20 age- and sex-matched normal controls from outside the endemic area. We tested for autoreactivity to several immunoglobulins and complement. Both human skin and bovine tail were used as antigens.

Results

We detected autoreactivity to neural structures, mechanoreceptors, nerves, perineural cell layers of the arachnoid envelope around the optic nerve, brain structures, and to neuromuscular spindles; these structures colocalized with several neural markers. The patient antibodies also colocalized with desmoplakins 1 and 2, with the armadillo repeat protein deleted in velo-cardio-facial syndrome and with p0071 antibodies. Autoreactivity was also found associated with neurovascular bundles innervating the skin, and immunoelectron microscopy using protein A gold against patient antibodies was positive against the nerve axons. Paucicellularity of the intraepidermal nerve endings and defragmentation of the neural plexus were seen in 70% of the cases and not in the controls from the endemic area (p < 0.005). Neuropsychological and/or behavioral symptoms were detected in individuals from the endemic area, including sensorimotor axonal neuropathy.

Conclusions

Our findings may explain for the first time the “pose of pemphigus,” representing a dorsiflexural posture seen in EPF patients vis-a-vis the weakness of the extensor nerves, and furthermore, the autoreactivity to nerves in EPF could explain the “burning sensation” encountered in EPF disease.

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Abbreviations

EPF:

Endemic pemphigus foliaceus

El Bagre-EPF:

endemic pemphigus foliaceus in El Bagre, Colombia

FS:

fogo selvagem

ICS:

intercellular stain between the keratynocytes

BMZ:

basement membrane zone

DIF and IIF:

direct and indirect immunofluorescence

ENFD:

epidermal nerve fiber density

SDI:

silver diamine ion stain

BP:

bullous pemphigoid

MBS:

modified Bielschowsky stain

NHP:

Nottingham Health Profile

LKS:

Lysholm Knee Scale

NDIC:

Normarski differential interference contrast confocal microscopy

IHC:

immunohistochemistry

CFM:

confocal microscopy

IB:

immunoblotting

IEM:

immunoelectron microscopy

ARVCF:

armadillo repeat protein deleted in velo-cardio-facial syndrome

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Acknowledgement

We thank Jonathan S. Jones, HT, and Lynn K. Nabers, HT, HTL for their expertise and excellent technical assistance at Georgia Dermatopathology Associates.

Funding sources

Georgia Dermatopathology Associates, Atlanta, GA, USA (MSH, AMAV). 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). Confocal studies were performed with funds from the Department of Ophthalmology, Emory University Medical Center, Atlanta, GA, USA (HG) (NIH NEI EY06360).

Author information

Authors and Affiliations

  1. Georgia Dermatopathology Associates, 1534 North Decatur Rd. NE, Suite 206, Atlanta, GA, 30307-1000, USA

    Ana Maria Abreu-Velez & Michael S. Howard

  2. Robert P. Apkarian Integrated Electron Microscopy Core, Emory University Medical Center, Atlanta, GA, USA

    Hong Yi

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

    Weiqing Gao & Hans E. Grossniklaus

  4. Department of Dermatology, School of Medicine, Kurume University, Kurume, Japan

    Takashi Hashimoto

Authors
  1. Ana Maria Abreu-Velez
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  2. Michael S. Howard
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  3. Hong Yi
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  4. Weiqing Gao
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  6. Hans E. Grossniklaus
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Correspondence to Ana Maria Abreu-Velez.

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Abreu-Velez, A.M., Howard, M.S., Yi, H. et al. Neural System Antigens Are Recognized by Autoantibodies from Patients Affected by a New Variant of Endemic Pemphigus Foliaceus in Colombia. J Clin Immunol 31, 356–368 (2011). https://doi.org/10.1007/s10875-010-9495-1

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