Project title: Detection of pre-clinical autoimmune disease

Mentor: Nancy J. Olsen MD

Other faculty: David R. Karp, MD, PhD
Ward Wakeland, PhD
Amy E. Wandstrat, PhD

Autoimmune diseases affect 5% of the population and can inflict significant morbidity and mortality on relatively young patients. Early detection of these illnesses prior to development of organ damage is the most promising approach to treatment and potential cure. We are interested primarily in ways to detect reliably the presence of rheumatoid arthritis and systemic lupus erythematosus in early or even pre-clinical phases. The Dallas Regional Autoimmune Disease Registry (DRADR) has been developed to enroll subjects for study. In addition to patients with RA, SLE and other autoimmune disorders, the registry enrolls first degree relatives and normal control subjects. This resource banks clinical information as well as biological samples for serologic, genetic and gene expression analyses. Studies in lupus have utilized autoantibody profiling to distinguish subgroups of patients and family members who are at high risk of disease (Wandstrat et al, J. Autoimm. 27:153, 2006). Other ongoing analyses are utilizing SNP typing in gene loci implicated in susceptibility to identify risk factors. In rheumatoid arthritis, antigen-specific responses to citrullinated peptides are being examined to determine changes in the immune repertoire that might precede disease. This is done within the context of the gene locus most highly correlated with RA, HLA-DR4. Additional investigations are examining the role of gene expression patterns in peripheral blood cells of RA and SLE patients as an approach to development of diagnostic blood tests that would assist the primary care physician in making more accurate early diagnoses and referrals for subspecialist care.