# PATHOPHYSIOLOGY OF EXPERIMENTALLY INDUCED PEMPHIGUS

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 1991 · $174,789

## Abstract

DESCRIPTION (Adapted from the applicant's abstract):  The long-term goals
of the principal investigator are definition of the pathogenic role of
pemphigus and pemphigoid autoantibodies in the production of cutaneous
lesions, primarily through the use of an in vivo murine model.

The investigators have recently identified a novel autoimmune blistering
mucocutaneous syndrome that is associated with underlying neoplasms that
they have termed paraneoplastic pemphigus.  They believe that their
preliminary studies support the following hypotheses regarding the etiology
of this syndrome.  (a) A subset of patients with blistering mucosal and
cutaneous lesions and underlying neoplasms have a clinically and
immunologically distinctive paraneoplastic syndrome.  (b) They have
autoantibodies that recognize a characteristic complex of epidermal
antigens, Mr 250 KD, 230 KD, 210 KD, and 190 KD, by immunoprecipitation of
metabolically labelled keratinocytes.  (c) The tumors of these patients
anomalously express antigens that are identical to or cross-reactive with
the epithelial antigens.  (d) The autoantibodies, directed primarily
against tumor antigens, bind to and cause lesions within the skin and
mucosa of the affected patients.  The investigators present preliminary
data showing that:  (1) The autoantibodies of all cases have similar
antigenic specificity; (2) the 250 KD Ag is desmoplakin 1 - a demonstrated
plaque protein - and the 230 KD Ag is the 230 KD bullous pemphigoid Ag a
hemidesmosomal protein; (3) the autoantibodies from these patients cause
cutaneous and esophageal lesions in vivo by passive transfer into mice; (4)
the tumor (a reticulum cell sarcoma) from one case possesses desmosomes and
expresses desmoplakin I, that is reactive with both a monoclonal antibody
against desmoplakin and the patients' serum autoantibodies.  This study
will examine the following points raised by these observations:  (1) To
define the specificity of the autoantibodies; (2) define the identity of
the 210 and 190 KD antigens; (3) define the precise nature of antigens
expressed by these tumors; (4) ascertain if these antigens are expressed
only in the tumors of affected individuals, and (5) define the mechanisms
by which the antibodies produce epithelial damage in vivo.  This they
believe is an unique opportunity to explore the complex relationship
between tumor immunity and autoimmunity, for this disease may represent
another biologic example in which immune response directed against tumor
antigens may cross-react with constitutive proteins of host tissue, with
disastrous "autoimmune" effects for the patient.

Finally, the investigators have defined a major immunogenic region (MIR) of
the 180 KD bullous pemphigoid antigen that is preferentially recognized by
patients with Herpes gestationis (HG) (gestational pemphigoid).  This is a
41-amino acid peptide that is bound by the majority of sera from affected
patients.  The investigators have preliminary data showing the BP 1...

## Key facts

- **NIH application ID:** 3156319
- **Project number:** 2R01AR032490-09
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **SAM.gov UEI:** FTMTDMBR29C7
- **Principal Investigator:** GRANT J ANHALT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $174,789
- **Award type:** 2
- **Project period:** 1983-08-01 → 1994-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3156319

## Citation

> US National Institutes of Health, RePORTER application 3156319, PATHOPHYSIOLOGY OF EXPERIMENTALLY INDUCED PEMPHIGUS (2R01AR032490-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3156319. Licensed CC0.

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