# RHEUMATOID FACTOR:  GENETICS, PATHOGENESIS, & MODULATION

> **NIH NIH R01** · SCRIPPS CLINIC AND RESEARCH FOUNDATION · 1988 · $234,378

## Abstract

Rheumatoid arthritis is an extravascular immune complex disease that
affects several million Americans.  The exact cause of the illness is
unknown.  However, IgM and IgG autoantibodies against IgG (rheumatoid
factors, RF), in the absence of exogenous antigens, form the largest
fraction of the complement-fixing immunoglobulin aggregates that are
abundant in rheumatoid synovial fluids.

Experiments from this laboratory have demonstrated the inheritance of
RF-associated private idiotypes in families of patients with rheumatoid
arthritis, and the sharing of idiotypes by the kappa light chains of RF's
from unrelated individuals.  Additionally, the investigations have shown
that IgM-RF precursors circulate in normal subjects at birth and are
frequent among the immature B lymphocytes of normal adults.  These results
have prompted us to suggest that the sustained production of RF in
rheumatoid patients, in the absence of any apparent exogenous stimulus, may
signify an underlying, abnormal regulation of B lymphocytes at early stages
of differentiation.

We now propose (1) to use newly developed and unique anti-idiotypic
reagents to elucidate how immunoglobulin structural genes influence RF
synthesis and fine specificity in normal and rheumatoid subjects, (2) to
determine the role of accessory T cells in the switch from IgM-RF to
IgG-RF, (3) to disclose the part played by autologous anti-idiotypic
antibody in the regulation of RF synthesis, and in the formation of immune
complexes, (4) to modify RF production with drugs that alter immature B
cell function, with anti-receptor antibodies, and by active immunization
with synthetic-hypervariable region peptides.

The experiments will help ascertain why IgM-RF and IgG-RF regularly develop
in rheumatoid patients, and will show how these normally protective
autoantibodies contribute to a self-perpetuating synovitis.  They may lead
to new modalities for the treatment of rheumatoid disease.

## Key facts

- **NIH application ID:** 3155319
- **Project number:** 5R01AR025443-10
- **Recipient organization:** SCRIPPS CLINIC AND RESEARCH FOUNDATION
- **Principal Investigator:** DENNIS CARSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $234,378
- **Award type:** 5
- **Project period:** 1979-09-01 → 1989-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155319

## Citation

> US National Institutes of Health, RePORTER application 3155319, RHEUMATOID FACTOR:  GENETICS, PATHOGENESIS, & MODULATION (5R01AR025443-10). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3155319. Licensed CC0.

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