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Journal of the American Academy of Dermatology
Volume 62, n° 3
pages 437-447 (mars 2010)
Doi : 10.1016/j.jaad.2009.06.007
accepted : 3 June 2009
Original Articles

Human eyelid meibomian glands and tarsal muscle are recognized by autoantibodies from patients affected by a new variant of endemic pemphigus foliaceus in El-Bagre, Colombia, South America
 

Ana Maria Abreu-Velez, MD, PhD a, , Michael S. Howard, MD a, Takashi Hashimoto, MD b, Hans E. Grossniklaus, MD c
a Georgia Dermatopathology Associates, Atlanta, Georgia 
b Department of Dermatology, Kurume University School of Medicine, Kurume, Japan 
c Department of Ophthalmology, Emory University Medical Center, Atlanta, Georgia 

Reprint requests: Ana Maria Abreu-Velez, MD, PhD, Georgia Dermatopathology Associates, 1534 N Decatur Rd NE, Suite 206, Atlanta, GA 30307-1000.
Abstract
Background

Previously, we described a new variant of endemic pemphigus foliaceus (EPF) in Colombia, South America (El Bagre-EPF).

Objective

Continuing our characterization of this variant of EPF, we now focus on one of our previously reported clinical findings: the presence of ocular lesions. These ocular lesions are seen in patients having extensive skin involvement, as measured by the Lund and Browder scale, which is generally used for patients with skin burns.

Methods

We specifically searched for evidence of autoreactivity to various eyelid structures in these patients and correlated our immunologic data with the clinical findings. We performed indirect immunofluorescence studies using normal-appearing human eyelid skin from routine blepharoplasties as substrate tissue. We tested sera from 12 patients with El Bagre-EPF and ocular lesions, 5 patients with sporadic (nonendemic) pemphigus foliaceus, and 20 healthy control subjects (10 from the El Bagre-EPF endemic area and 10 from nonendemic areas). We used fluorescein isothiocyanate conjugated goat antiserum to human total IgG/IgA/IgM as a secondary antibody. In addition, we used fluorescein isothiocyanate conjugated antibodies to human fibrinogen, albumin, IgG, IgE, C1q, and C3, Texas Red (Rockland Immunochemicals, Inc, Gilbertsville, PA), Alexa Fluor 555, or Alexa Fluor 594 (Invitrogen, Carlsbad, CA). Ki-67 (a cell proliferation marker) was used to determine the cell proliferation rate, and nuclear counterstaining was performed with either 4′, 6-diamidino-2-phenylindole or Topro III (Invitrogen, Carlsbad, CA).

Results

We observed autoreactivity to multiple eyelid structures, including meibomian glands and tarsal muscle bundles at different levels, and some areas of the epidermis and the dermis close to the isthmus of the eyelids. Tarsal plate autoreactivity was seen in 10 of 12 of the El Bagre-EPF sera and in one control with pemphigus erythematosus. Furthermore, immunoprecipitation using an eyelid sample as a substrate with 1 mmol/L of sodium orthovanodate showed autoreactivity to several antigens, including some of possible lipid origin.

Limitations

The main limitation of this study is the fact that the antigen or antigens remain unknown.

Conclusion

We identified for the first time to our knowledge autoantibodies to meibomian glands and tarsal muscle in El Bagre-EPF. Our findings suggest that the autoantibodies to the ocular structures cause the clinical and histopathological findings in the ocular lesions in El Bagre-EPF.

The full text of this article is available in PDF format.

Key words : autoimmunity, endemic pemphigus foliaceus, meibomian glands, tarsal muscle

Abbreviations used : BMZ, Dsg, EPF, FITC, FS, IB, IC, IF, IP, PBS, PE, PF, SDS



 Supported by Georgia Dermatopathology Associates (Dr Howard). The El Bagre-endemic pemphigus foliaceus samples were collected with the support of previous grants from the Embassy of Japan in Bogota, Colombia, (Dirección Seccional de Salud de Antioquia), U. de A, Mineros SA (anonymous society) (SA) (Dr Abreu-Velez), Medellin, Colombia, South America, and Emory University Medical Center (Dr Grossniklaus). Our studies were also funded by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and by a grant from the Ministry of Health, Labor and Welfare (Research on Intractable Diseases [Dr Hashimoto]).
 Conflicts of interest: None declared.



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