# PATHOGENIC ANTI-DNA AUTOANTIAB-REGULATION IN HUMAN LUPUS

> **NIH NIH R01** · TUFTS MEDICAL CENTER · 1992 · $129,898

## Abstract

DESCRIPTION:   (Adapted from  Applicant's Abstract)   The investigator's
long term  goal is to  define the fundamental mechanism  of the prototypic
systemic autoimmune  disease,  Systemic LupusErythematosus  (SLE).
Theetiological mechanism of SLE remains elusive because the primary
antigen that triggers the pathogenic  autoimmune response in this disease
is  unknown.  In spite of this obstacle,  the investigators have cloned
the select T-helper cells that induce the production of the pathogenic
variety of anti-DNA  autoanitbodies in SLE.

Analysis  of the  structure and  specificities of the receptors  expressed
by these  particular T-cells  and the  pathogenic autoantibody  producing
B-cells that are representative of the disease, as well as studies of
their regulation may lead  to an understanding of  the etiologic mechanism
of  lupus in humans. The specific goals of this application  involve: (1)
PATHOGENIC T-CELLS:   (a) Determine the  V region  sequences of the
receptors  (TcRs) expressed  by the pathogenic  anti-DNA  autoantibody-
inducing  T-cells from lupus  patients  to detect any clonal
restriction/recurrent usage or any special featuure in their junctional
region  (CDR3)  sequences that  would  provide  clues for  their antigenic
specificities.   (b)  Determine the specificities of these  lupus T-
helper  cells  that  preferentially  interact  with  pathogenic
autoantibody- producing B-cells, using synthetic peptides and autologous
B-cell clones. (c) Determine the in  vivo pathogenic relevance of
theseautoimmune T-helper cell clones using immunodeficient SCID mice.  (2)
PATHOGENIC B-CELLS: (a) Clone human lupus B-cells that produce pathogenic
anti-DNA autoantibodies of IgG class and cationic charge.  Determine the
in  vivo pathogenic relevance of such autoantibodies and their
representation in human lupus nephritis. (b) Define the structural basis
of cationic charge, antigenic specificities, idiotypic cross-reactions and
clonalrelationships among the pathogenic anti- DNA autoantibodies.   (c)
Define the intrinsic B-cell defect in SLE that leads to an excessive
production of heat shock proteins.  These studies will help us todesign
specific therapies that would intervene  in the basic steps leading to
systemic autoimmune disease.

## Key facts

- **NIH application ID:** 3159132
- **Project number:** 2R01AR039157-04
- **Recipient organization:** TUFTS MEDICAL CENTER
- **SAM.gov UEI:** MY2ERHGDV956
- **Principal Investigator:** SYAMAL K DATTA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $129,898
- **Award type:** 2
- **Project period:** 1989-06-15 → 1993-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3159132

## Citation

> US National Institutes of Health, RePORTER application 3159132, PATHOGENIC ANTI-DNA AUTOANTIAB-REGULATION IN HUMAN LUPUS (2R01AR039157-04). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3159132. Licensed CC0.

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