# THE IMMUNE RESPONSE IN HUMAN AUTOIMMUNE DISEASES

> **NIH NIH R01** · SCRIPPS CLINIC AND RESEARCH FOUNDATION · 1987 · $163,042

## Abstract

Sjogren's syndrome (SS) is a chronic autoimmune disease characterized by
lymphocytic infiltration of lacrimal and salivary glands.  These patients
have markedly increased frequency of lymphadenopathy, circulating
paraproteins, and risk of developing non-Hodgkin's lymphoma.  Rheumatoid
factor (anti-IgG) in the sera of SS patients contains a cross reactive
idiotype (CRI) defined by a monoclonal antibody and by synthetic peptides
derived from VKappa IIIb light chains.  The CRI is shared with RF
paraproteins from patients with Waldenstrom's macroglobulinemia.  CRI+ B
cells in salivary gland (SG) biopsies of SS patients can be detected in
high frequency and we have observed two CRI+ lymphomas that arose in the
setting of pre-existing SS.  In order to examine at the cellular and
molecular level the events associated with lymphoid infiltration of the SG
and the regulation of autoantibody synthesis, we will:

1. Establish whether the high frequency of CRI expression in SG of SS
patients results from expansion of a lymphoid subset utilizing a single
variable region gene family.  We will examine DNA from B cell hybridomas
derived from SG biopsies and compare these variable regions to "germ line"
DNA from the same individuals.

2. Determine whether T cell infiltrates in SG biopsies are monoclonal or
oligoclonal in origin by analyzing DNA from SG biopsies and from T cell
hybridomas derived from these tissue lesions.

3. Assess the role of Epstein Barr virus (EBV) in CRI induction and the
regulation of CRI synthesis by specific T cell subsets.  We are
concentrating on this virus based on our recent finding that EBV is
reactivated in the SG of SS patients.

The proposed studies will use a molecular biological approach to
characterize the B cells, T cells, and putative antigens contributing to a
well defined human autoimmune disease.

## Key facts

- **NIH application ID:** 3156708
- **Project number:** 2R01AR033983-07
- **Recipient organization:** SCRIPPS CLINIC AND RESEARCH FOUNDATION
- **Principal Investigator:** ROBERT IRVING FOX
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $163,042
- **Award type:** 2
- **Project period:** 1980-06-01 → 1992-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3156708

## Citation

> US National Institutes of Health, RePORTER application 3156708, THE IMMUNE RESPONSE IN HUMAN AUTOIMMUNE DISEASES (2R01AR033983-07). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3156708. Licensed CC0.

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