# ETIOLOGY AND PATHOGENESIS OF PEMPHIGUS

> **NIH NIH R01** · MEDICAL COLLEGE OF WISCONSIN · 1993 · $215,676

## Abstract

It represents a comprehensive approach to study Brazilian pemphigus
foliaceus or Fogo Selvagem (FS) and describes a series of protocols aimed
at uncovering the etiology of this autoimmune disease.  During the previous
funding period we have accumulated substantial original information which
is applicable not only to understanding the pathogenesis of FS but is also
relevant to other aspects of keratinocyte biology and biochemistry, i.e.,
we have shown that FS autoantibodies are pathogenic and restricted to the
IgG4 subclass.  FS autoantibodies appear to induce keratinocyte detachment
by impairing the function of desmoglein 1 (a cadherin-like desmosomal
glycoprotein) which is the epidermal antigen recognized by these
antibodies.  This proposal also describes two novel autoantibody systems in
FS sera:  IgG2 autoantibodies against keratin-10 and autoantibodies against
a ubiquitin-carrier protein.  The relevance of these autoantibodies in the
etiology and pathogenesis of FS will be investigated in this proposal.
Based on epidemiological data, this grant addresses the hypothesis that the
humoral autoimmune response in FS is triggered and maintained by an
environmental "antigenic factor(s)".  FS is the ideal, and perhaps the
only, human autoimmune disease in which this hypothesis could be tested
since it is endemic to certain regions of Brazil, where there are currently
more than 15,000 registered cases.  Individuals at risk are outdoor workers
living on agricultural farms.  Our studies show that individuals developing
FS share distinctive susceptibility HLA DR1 alleles and lack a dominant
DQw2 protective gene which is present in normal people.  Susceptible
individuals, therefore, if exposed to unique environmental antigens, may
produce antibodies which, in turn, cross-react with keratinocyte surface
epitope(s) and cause acantholysis ("antigenic mimicry"?).  Among a variety
of etiological agents, an insect vector (a "black fly", family Simuliidae)
has been suspected of precipitating the disease.  Several circumstantial
observations, and a recent epidemiologic case-control study (see Progress
Report Section), support this hypothesis.  This proposal will
systematically investigate the role of black flies as a potential source of
sensitizing agent that leads to autoantibody formation in FS.  If
successful, the information derived from these studies should be relevant
to other human autoimmune diseases.

## Key facts

- **NIH application ID:** 3156359
- **Project number:** 5R01AR032599-11
- **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:** 1993
- **Award amount:** $215,676
- **Award type:** 5
- **Project period:** 1988-07-01 → 1996-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3156359

## Citation

> US National Institutes of Health, RePORTER application 3156359, ETIOLOGY AND PATHOGENESIS OF PEMPHIGUS (5R01AR032599-11). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3156359. Licensed CC0.

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