# HLA CLASS 11 VARIANTS IN DR4+ RHEUMATOID ARTHRITIS

> **NIH NIH R01** · BENAROYA RESEARCH INST AT VIRGINIA MASON · 1988 · $150,852

## Abstract

Although the genetic basis of complex diseases such as RA is likely to be
multifactorial, the strong HLA-DR4 association with RA suggests that one of
the contributing genetic features is encoded within HLA.  Our previous work
documents extensive structural and genotypic diversity of class II
molecules among different normal DR4+ individuals.  At least six different
haplotypes, differing in gene products of at least three class II loci, all
share the HLA-DR4 specificity, even though they are considered
phenotypically identical by standard typing and disease association
studies.  It is now appropriate to reconsider the association between
HLA-DR4 and RA in terms of a more comprehensive molecular context.

In preliminary studies among DR4+ patients with seropositive JRA, a
striking prevalence of two specific DR4+ haplotypes has been found.  Using
a panel of locus-specific monoclonal antibodies which distinguish the
products of three separate class II loci on these two haplotypes we will
evaluate molecular variants by 2-D gels, by peptide mapping, and by
analysis of combinatorial associations for each of the different class II
products linked to DR4.  Substantial DNA variation within HLA class II
genes also is observed among DR4+ haplotypes; to examine whether any such
polymorphisms represent consistent predictive markers for DR4+ haplotypes
in RA, we will extend these studies to JRA and adult RA populations
analyzed both by RFLP with DR, DQ, and DP cDNA probes, and by B1 exon
sequencing techniques.

These studies will yield a molecular fingerprint, both at the genomic and
the polypeptide level, for a series of class II molecules present on DR4+
haplotypes in patients and normals.  Such information is crucial for a more
critical perspective on the issue of HLA and disease, and will also
contribute to a number of basic clinical and immunogenetic questions
currently unresolved.

## Key facts

- **NIH application ID:** 3158012
- **Project number:** 5R01AR037296-03
- **Recipient organization:** BENAROYA RESEARCH INST AT VIRGINIA MASON
- **SAM.gov UEI:** PK9FMGRDRVD5
- **Principal Investigator:** GERALD T NEPOM
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $150,852
- **Award type:** 5
- **Project period:** 1986-01-01 → 1988-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3158012

## Citation

> US National Institutes of Health, RePORTER application 3158012, HLA CLASS 11 VARIANTS IN DR4+ RHEUMATOID ARTHRITIS (5R01AR037296-03). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3158012. Licensed CC0.

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