# THE LOCAL IMMUNE RESPONSE IN RHEUMATOID SYNOVITIS

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 1988 · $105,924

## Abstract

Using isoelectric focusing (IEF) this laboratory has found oligoclonal IgG
in 55% of synovial culture supernatants, and in 17% of RA sera or matched
synovial fluid (Arth Rheum 27:  976,1984).  In other studies this
oligoclonal serum IgG and the RA synovial culture IgG with a common
isoelectric point have been shown to share idiotypic (Id)
cross-reactivity.  Since anti-Id reagents provide one of the most powerful
and specific ways of establishing the common identity of antibodies, and
are often cross-reactive with antibodies of unrelated individuals directed
against the same antigen, they will be used to predict the nature of the
stimulating antigen(s) in RA.  Anti-Id antibodies will be produced in mice
(monoclonal), and in rabbits (polyclonal) against highly-purified,
oligoclonal bands of RA synovial IgG.  Monoclonal anti-Id will be bound to
an immunoadsorbent to isolate larger amounts of cross-reacting IgG from the
serum of the patient donating the synovium.  This cross-reactive serum IgG
will be used to screen viral, bacterial, and food antigens for reactivity
which would link them to the pathogenesis of RA.  Appropriately absorbed
rabbit anti-Id will be used to screen the IgG of other RA synovial cultures
or sera for cross-reactive idiotypic determinants which, if present, would
suggest a common cause for RA in different patients.  Rabbit anti-Id will
also be used to screen serum IgG (of non-RA patients) known to contain high
titers of antibodies agaist defined viral, bacterial, or food antigens to
detect Id cross- reactivity.  Such cross-reactivity with antibodies against
any of these antigens would provide a potential link to the immune stimulus
in RA.  In a patient with Id cross-reactivity, rabbit anti-Id can be used
to measure the reactive IgG in RA serum or synovial fluid to correlate its
concentration with changes in disease activity and/or response to therapy.

The upper 0.1 mm of RA cartilage contains IgG, IgM, and C3 in insoluble
form, compatible with IC.  Similar IC are found in the vacuoles of
polymorphonuclear leukocytes in synovial fluid.  IC will be isolated from
both sources to detect non-Ig and non-complement antigens capable of
stimulating the adjacent synovium.  Cartilage will also be stained using
F(ab)'2 fragments (not reactive with rheumatoid factors) of fluorescein or
peroxidase-labeled rabbit anti-Id to link the trapped IgG to that being
produced in the adjacent synovium.

## Key facts

- **NIH application ID:** 3157548
- **Project number:** 5R01AR036323-03
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **SAM.gov UEI:** YZJ6DKPM4W63
- **Principal Investigator:** WAYNE L HOFFMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $105,924
- **Award type:** 5
- **Project period:** 1986-01-01 → 1988-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3157548

## Citation

> US National Institutes of Health, RePORTER application 3157548, THE LOCAL IMMUNE RESPONSE IN RHEUMATOID SYNOVITIS (5R01AR036323-03). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3157548. Licensed CC0.

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