Animal models demonstrate different genetic factors which influence predisposition to autoimmune disease and the timing of disease onset. The autoimmune disorder of the MRL murine strain resembles SLE. The lpr (lymphoproliferative) mutation in the murine Fas gene accelerates the onset of lupus in MRL-lpr/lpr mice. There are genetic influences on susceptibility to human SLE. Early onset of human lupus also occurs. Although environmental accelerating factors have not been excluded, a genetic component to accelerated or early onset SLE is suggested by its predominance in some ethnic groups.African-Americans develop SLE at a significantly younger age than do U.S. Caucasians. In addition to the lupus-like disease MRL-lpr/lpr mice also develop a unique lymphoproliferative disease which has its human counterpart in a childhood onset syndrome. The investigators will test the hypothesis that polymorphism in the human Fas gene predisposes to the human analogs of MRL-lpr/lpr syndromes, early onset SLE, and juvenile lpr disease.
The specific aims outline strategies to accomplish this goal: (1) Does the Fas polymorphism associated with early onset SLE in Blacks correlate with age of SLE onset in other ethnic groups and with juvenile lpr disease? (2) What is the a) the molecular basis for this Fas polymorphism and b) its functional correlate(s)? (3) What is the mode of inheritance of the Fas polymorphism? and (4) How does the genomic organization of the human Fas gene compare in normal individuals and those with SLE and juvenile lpr disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR043523-02
Application #
2083230
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1994-09-30
Project End
1997-05-31
Budget Start
1995-09-01
Budget End
1996-05-31
Support Year
2
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Immune Disease Institute, Inc.
Department
Type
DUNS #
115524410
City
Boston
State
MA
Country
United States
Zip Code
02115
Rajsbaum, R; Fici, D; Fraser, P A et al. (2001) Polymorphism of the human retinoid X receptor beta and linkage disequilibrium with HLA-DPB1. Tissue Antigens 58:24-9
Fraser, P A; Lu, L Y; DeCeulaer, K et al. (1999) CD4 TCRBV CDR3 analysis in prevalent SLE cases from two ethnic groups. Lupus 8:311-9