# ETIOLOGY OF RHEUMATOID ARTHRITIS

> **NIH NIH R01** · STATE UNIVERSITY NEW YORK STONY BROOK · 1993 · $164,783

## Abstract

There has long been evidence that RA and related chronic arthritides
involve both genetic and infectious etiopathogenetic factors. Recently,
increased attention has focusing on the role of infectious agents
suspected of involvement.

In the past, an immense effort has been made to detect such agents in
these disorders using chiefly culture and immunologic methods, without
notable success. These approaches suffer from the need for prior knowledge
about the growth requirements or immunology of the organisms being sought
and therefore have been narrow in scope. Thus, the many negative results
obtained cannot easily be interpreted. To justify another such effort it
is necessary to overcome these limitations. The present approach is
believed largely to achieve this. It employs the polymerase chain reaction
with primers capable of amplifying essentially all known bacteria, which,
as detected by this method, includes the Chlamydiae, Rickettsiae and
mycoplasmas, along with essentially all other prokaryotes of medical
interest. This method, as we had originally proposed it, was since applied
by two groups, to the successful identification the causative agents in
two previously idiopathic diseases, Whippel's disease and bacillary
granulomatosis, thus clearly validating our original rationale. To apply
this approach to RA, we had first to resolve the problem of contamination,
the chief limitation to achieving the theoretical sensitivity of the PcR.
By succeeding with this we are now able to achieve sensitivity of 1
organism per reaction in practice in clinical specimens. Thus this method
can now provide significant information about both the presence and
absence of bacterial DNA in synovial specimens. Recent studies have
explored extending the generic bacterial PCR to an in situ method that
will allow a clear distinction between potential pathogens and
contaminants and will also provide insight into the histologic context of
any detected amplimers. The combination of these approaches should provide
a powerful means of obtaining unambiguous information about the presence
or absence of biologically relevant bacteria in RA synovial specimens. In
this way the hypothesis that persistent synovial infection is necessary
for maintenance of active rheumatoid synovitis will be tested, as will
more complex hypotheses addressing bacterial involvement in RA. Analogous.
studies of the HLA B27-related disorders and their association with
bacterial infection are also proposed.

## Key facts

- **NIH application ID:** 3156550
- **Project number:** 2R01AR033278-10
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **SAM.gov UEI:** M746VC6XMNH9
- **Principal Investigator:** CHARLES R STEINMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $164,783
- **Award type:** 2
- **Project period:** 1990-09-01 → 1998-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3156550

## Citation

> US National Institutes of Health, RePORTER application 3156550, ETIOLOGY OF RHEUMATOID ARTHRITIS (2R01AR033278-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3156550. Licensed CC0.

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