# NUCLEAR ACIDIC PROTEIN ANTIGENS IN RHEUMATIC DISEASES

> **NIH NIH R01** · UNIVERSITY OF MISSOURI-COLUMBIA · 1988 · $177,714

## Abstract

The objective is to elucidate the roles of nuclear acidic protein antigens
and certain other antigens in rheumatic diseases and in basic cellular
biology.  Patient autoimmune antibodies directed against distinct antigens
(RNP, Sm and Me) of the ubiquitous U1 small nuclear ribonucleoprotein
particle (U1 snRNP) are strongly associated with connnective tissue
diseases, ie. mixed connective tissue disease (MCTD), systemic lupus
erythematosus (SLE), and undifferentiated connective tissue disease (UCTD),
respctively.  Autoantigens (RNP, Sm, Me, etc.) and their five-nine
component peptides (9-70 Kdaltons), monospecific patient sera, IgG, and
murine and human monoclonal antibodes will be isolated by high performance
liquid chromatography ion, exchange, gel filtration, and immunoaffinity
chromatography, and by gel electrophoresis.  Antigens and autoantibodies
will be vigorously characterized by immunological (Ouchterlony, passive
hemagglutination, hemagglutination inhibition, competitive hemagglutination
inhibition, immunofluorescence, counter immunoelectrophoresis, ELISA, dot,
and Western blot) and biochemical (gel electrophoresis, nucleoside and
amino acid compositions, sugar and lipid analysis, RNA and amino acid
sequencing) methods.  Autoantigenic determinants of the U1 RNP and the
other anRNP peptides will be defined in terms of amino acid sequence, sugar
and lipid compositions, and compared to all known peptide sequences to
reveal any relationships to known viral, or "housekeeping" proteins.  The
9-14K dalton Sm antigenic peptides are of particular interest because they
are recognized by anti-histone monoclonal antibodies developed from
autoimmune MRL mouse hybridomas.  The question of the immunogenicity of the
defined antigenic determinants is central to understanding these autoimmune
responses and will be addressed.  Cellular localization and
co-localizations of the antigens with regard to function in RNA splicing
will be investigated by sophisticated high resolution digitized image
immunofluorescence microscopy.  Alterations in the antigen locations
throughout the cel cycle and during transcriptional inhibition will also be
evaluated.  Co-localization studies will be complemented by biochemical
reconstitution studies of the ineractions of snRNPs with hnRNPs for
recognition of intron sequences.  The heterogeneity of the human autoimmune
response will be investigated by various methods including description of
individual, specific peptide recognition by patient sera and the production
of a human monoclonal antibody library.  Human monoclonals will be produced
through either EBV transformation or myeloma/lymphoblastoid cell fusions.
The product of autoimmune response, the immune complex, will be
biochemically characterized and its distribution studied for specific
autoantibody-antigen reactivities.

## Key facts

- **NIH application ID:** 3155108
- **Project number:** 5R01AR020305-12
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **SAM.gov UEI:** SZPJL5ZRCLF4
- **Principal Investigator:** GORDON C. SHARP
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $177,714
- **Award type:** 5
- **Project period:** 1977-08-01 → 1991-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155108

## Citation

> US National Institutes of Health, RePORTER application 3155108, NUCLEAR ACIDIC PROTEIN ANTIGENS IN RHEUMATIC DISEASES (5R01AR020305-12). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3155108. Licensed CC0.

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