# ETIOLOGY AND PATHOGENESIS OF PEMPHIGUS

> **NIH NIH R01** · MEDICAL COLLEGE OF WISCONSIN · 1988 · $69,668

## Abstract

We have demonstrated that the autoantibodies produced by patients with
Pemphigus Vulgaris and Fogo Selvagem are pathogenic and are responsible for
inducing the disease in humans.  This has established the true autoimmune
nature of these diseases of obscure etiology.  We have selected Fogo
Selvagem to investigate the etiology of pemphigus because of its unique
epidemiology, i.e., it is endemic in certain regions of Brazil, where there
are currently more than 10,000 registered cases.  In comparison, pemphigus
in North America is very rare.  The affected population includes farmers,
children and young adults of all ethnic groups.  The disease has a striking
epidemiology that strongly implicates an infectious "agent", transmitted by
an insect vector (a fly of the genus Simulium).

We include 3 Specific Aims in this Proposal.  (a) The first aim describes
the evaluation of the titers of pemphigus autoantibodies in patients and
controls from endemic and nonendemic areas in Brazil.  (b) The second study
will examine the incidence and prevalence of a new autoantibody system
discovered in the sera of two patients with Fogo Selvagem (designated as
Cascas-42).  This autoantibody is highly specific for the 56.5 K murine
keratin and decorates the cell surface of keratinocytes, suggesting that it
recognizes an extracellular domain of this keratin.  (c) The third aim will
study "foreign antigens" in the epidermis and sera of patients as well as
in extracts made of the insects (Simulium) which are suspected to be
vectors of Fogo Selvagem.

We believe now that the systematic study of Fogo Selvagem as described in
this grant will establish the foundations which may culminate in the
identification of the etiological agent of this autoimmune disease.  If we
accomplish this goal, it would probably represent the first study that
establishes an etiology for a human autoimmune disease.  Equally important
perhaps, these studies may present new concepts in keratin biology.  We
have evidence that certain keratins may have domains, inserted into the
cell membrane (transmembrane?) that are exposed on the keratinocyte surface
where they become entangled with similar structures of neighboring cells to
form an "exoskeleton" which is located in the epidermal intercellular
spaces and linked to the keratinocyte cytoskeleton.  This
exoskeleton-cytoskeleton framework may provide structural support to the
whole epidermis.

## Key facts

- **NIH application ID:** 3156360
- **Project number:** 7R01AR032599-06
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **SAM.gov UEI:** E8VWJXMMUQ67
- **Principal Investigator:** Luis A. Diaz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $69,668
- **Award type:** 7
- **Project period:** 1988-07-01 → 1991-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3156360

## Citation

> US National Institutes of Health, RePORTER application 3156360, ETIOLOGY AND PATHOGENESIS OF PEMPHIGUS (7R01AR032599-06). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3156360. Licensed CC0.

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