# AUTOANTIBODIES IN SCLERODERMA AND RAYNAUD'S PHENOMENON

> **NIH NIH R01** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 1988 · $154,070

## Abstract

Anticentromere antibodies (ACA) present in sera from patients with CREST or
Raynaud's phenomenon with or without a connective tissue disease or in
Raynaud's disease have been found to react with 3 centromeric proteins
(CENPs):  CENP-A, CENP-B and CENP-C.  CENP-B which appears to be the major
autoantigen has been cloned and is expressed in E. coli.  Anti-Scl-70 has
been shown to react with topoisomerase I which has also been cloned.  Using
immunoblotting technique, anti-toposomerase I can be demonstrated in sera
negative for anti-SCL-70 on immunodiffusion.  Preliminary data suggests
that the presence of anti-topoisomerase I may predict the development of
scleroderma and that anti-CENP-B may predict the development of CREST
syndrome.

The presence of antibodies to the 3 centromeric proteins and topoisomerase
I will be studied by immunoblotting with chromosomes.  The level of
anti-CENP-B and topoisomerase I will be studied by ELISA assay using the
fusion protein CENP-B and topoisomerase I.

We postulate that there is a common genetic background in patients with
these autoantibodies which can be demonstrated by looking for the presence
of cross reactive idiotypes.  Affinity purified auto-antibodies to CENP-B
and to topoisomerase I and autoantibodies to CENP-B and topoisomerase I
generated by human-human hybridomas will be used to produce polyclonal
anti-idiotypes in rabbits and monoclonal anti-idiotypes in mice.  We will
look for cross reactive idiotypes in sera from patients and their
relatives.  Sera containing cross reactive idiotype will be studied using
electrofocusing and labelled antigen to determine whether or not the cross
reactive idiotype reacts with antigen.

A prospective study of patients with Raynaud's phenomenon unassociated at
the onset with a connective tissue disease will be carried out to determine
the clinical significance of the presence and amount of anti-CENP-B and
topoisomerase I.  In addition, the prognostic significance of the presence
of anti-CENP-A and anti-CENP-C will be determined.

## Key facts

- **NIH application ID:** 3158364
- **Project number:** 5R01AR037986-02
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **SAM.gov UEI:** H6D6JMXJXDE6
- **Principal Investigator:** Naomi F. Rothfield
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $154,070
- **Award type:** 5
- **Project period:** 1986-12-01 → 1989-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3158364

## Citation

> US National Institutes of Health, RePORTER application 3158364, AUTOANTIBODIES IN SCLERODERMA AND RAYNAUD'S PHENOMENON (5R01AR037986-02). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3158364. Licensed CC0.

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