# MOLECULAR GENETICS OF AUTOANTIBODIES IN HUMANS

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 1990 · $103,205

## Abstract

Autoantibodies are antibodies which react with self components, and
occur not only in patients with autoimmune diseases but also in
some normal subject, suggesting that autoantibodies may have some
pathologic as well as physiologic roles.  Recently, anti-idiotypic
reagents were generated by immunization with synthetic peptides
corresponding to the hypervariable regions of some human monoclonal
anti-IgG antibodies (rheumatoid factors, RFs).  These
anti-idiotypes detected two "primary structure-dependent"
crossreactive idiotypes (CRIs) on 80% human monoclonal RFs,
indicating that the majority of these RFs are encoded by single
light chain variable region gene, designated Vk(RF).  Indeed, the
putative Vk gene was cloned from a normal human placenta and was
found to be identical with four human RF light chains.  Very
recently, the cloned Vk(RF) gene was shown to used by a significant
portion of RFs in most patients with Sjogren's syndrome (SS).

Thus, using CRI positive RFs in SS patients as a model system,
the overall objectives are to identify and characterize all Ig gene
elements required for RF activities, to define the polymorphisms
of these RF-related genes in human populations, to analyze the RF
gene products and to delineate the molecular basic of RF production
in SS patients and control normals.  Specifically, (i) RF-secreting
cell lines will be generated from SS patients with high titers of
CRI+ RFs transformation with Epstein Barr virus and/or fusion with
appropriate partners.   Then, their specific rearranged heavy and
light chain variable region genes will cloned and characterized.
Subsequently, the corresponding germline gene segments will be
identified and studied.  (ii) B cell lines from SS patients and
normals will be established to provide unlimited supply of genomic
DNA, which will analyzed for restriction fragment length
polymorphisms (RFLPs) of the RF-related genes.  (iii) Sequence-
specific antibodies will be induced with synthetic peptides
corresponding to the characteristic regions of RF-genes, and will
be applied characterize the RF-gene products in humans.
Furthermore, plasmids will constructed to elucidate the cis- and
trans-regulatory factors involved regulating expression of the
RF-genes in SS patients.

## Key facts

- **NIH application ID:** 3159099
- **Project number:** 7R01AR039039-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **SAM.gov UEI:** UYTTZT6G9DT1
- **Principal Investigator:** POJEN P CHEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $103,205
- **Award type:** 7
- **Project period:** 1990-07-01 → 1991-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3159099

## Citation

> US National Institutes of Health, RePORTER application 3159099, MOLECULAR GENETICS OF AUTOANTIBODIES IN HUMANS (7R01AR039039-04). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3159099. Licensed CC0.

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