Epidemiologic studies support a genetic basis for susceptibility to human SLE. New information from genetically defined murine models of systemic lupus also support the view of a complex, polygenic disease with a threshold liability for inheritance. These studies in """"""""lupus-like"""""""" mice suggest that different genes may control different aspects of the """"""""lupus"""""""" phenotypes. Most importantly, these studies coupled with the rapid advances in knowledge available through the human genome project, underscore the feasibility of using the tools of modern genetics in defining human disease susceptibility and severity. The approach to the genetics of human SLE requires a multi-disciplinary, team effort. Within this SCOR, we have assembled a unique and exceptionally strong multi-disciplinary team which leverages both fundamental and clinical investigations and SLE at the host institution and at the partner institutions. Our team expertise includes mastery of the theory and techniques of modern genetic mapping (linkage), full appreciation of the SLE clinical phenotypes and the proven ability to recruit and maintain cohorts of SLE patients (sib-pairs, multiplex families, simplex families and longitudinal cohorts). Uniting this expertise is a deep appreciation for the pathophysiological processes in SLE in order to facilitate the selection of candidate genes and to translate findings into meaningful, mechanism-based clinical intervention. Through our team effort, we have an unprecedented power to accelerate the pace of discovery, to replicate and confirm regions of linkage, to narrow regions of interest, to pursue the structure and biology of candidate genes, and to test the relevance of these discoveries to clinical phenotype in a very large, meticulously studied cohort of SLE patients. Our efforts will advance our understanding of SLE and leverage both the application and current therapy and the development of new, mechanism based therapies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Specialized Center (P50)
Project #
5P50AR045231-04
Application #
6375101
Study Section
Special Emphasis Panel (ZAR1-AAA-C (J2))
Program Officer
Freeman, Julia B
Project Start
1998-07-01
Project End
2004-06-30
Budget Start
2001-07-01
Budget End
2004-06-30
Support Year
4
Fiscal Year
2001
Total Cost
$1,115,018
Indirect Cost
Name
University of Alabama Birmingham
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Vaughn, Samuel E; Kottyan, Leah C; Munroe, Melissa E et al. (2012) Genetic susceptibility to lupus: the biological basis of genetic risk found in B cell signaling pathways. J Leukoc Biol 92:577-91
Heinlen, Latisha D; Ritterhouse, Lauren L; McClain, Micah T et al. (2010) Ribosomal P autoantibodies are present before SLE onset and are directed against non-C-terminal peptides. J Mol Med (Berl) 88:719-27
Burgos, Paula I; Perkins, Elizabeth L; Pons-Estel, Guillermo J et al. (2009) Risk factors and impact of recurrent lupus nephritis in patients with systemic lupus erythematosus undergoing renal transplantation: data from a single US institution. Arthritis Rheum 60:2757-66
McClain, Micah T; Heinlen, Latisha D; Dennis, Gregory J et al. (2005) Early events in lupus humoral autoimmunity suggest initiation through molecular mimicry. Nat Med 11:85-9
Bruner, Benjamin F; Wynn, Donny M; Reichlin, Morris et al. (2005) Humoral antigenic targets of the ribosomal P0 lupus autoantigen are not limited to the carboxyl region. Ann N Y Acad Sci 1051:390-403
Su, Kaihong; Li, Xiaoli; Edberg, Jeffrey C et al. (2004) A promoter haplotype of the immunoreceptor tyrosine-based inhibitory motif-bearing FcgammaRIIb alters receptor expression and associates with autoimmunity. II. Differential binding of GATA4 and Yin-Yang1 transcription factors and correlated receptor expre J Immunol 172:7192-9
McClain, Micah T; Arbuckle, Melissa R; Heinlen, Latisha D et al. (2004) The prevalence, onset, and clinical significance of antiphospholipid antibodies prior to diagnosis of systemic lupus erythematosus. Arthritis Rheum 50:1226-32
McClain, Micah T; Lutz, Carol S; Kaufman, Kenneth M et al. (2004) Structural availability influences the capacity of autoantigenic epitopes to induce a widespread lupus-like autoimmune response. Proc Natl Acad Sci U S A 101:3551-6
Su, Kaihong; Wu, Jianming; Edberg, Jeffrey C et al. (2004) A promoter haplotype of the immunoreceptor tyrosine-based inhibitory motif-bearing FcgammaRIIb alters receptor expression and associates with autoimmunity. I. Regulatory FCGR2B polymorphisms and their association with systemic lupus erythematosus. J Immunol 172:7186-91
Nath, Swapan K; Namjou, Bahram; Kilpatrick, Jeff et al. (2004) A candidate region on 11p13 for systemic lupus erythematosus: a linkage identified in African-American families. J Investig Dermatol Symp Proc 9:64-7

Showing the most recent 10 out of 47 publications