Ankylosing Spondylitis (AS)
This study is being conducted because 1% of the world’s population has axial spondyloarthritis (SpA). The study has found 12+ new genes, and the first gene-gene interaction (ERAP1 restricted to HLA-B27) invoking peptide presentation; we have confirmed USA epidemiology of SpA (1%) and inflammatory back pain (6%); and HLA-B27 reduction with age, as well as positive treatment effects of anti-TNF agents. In the future, we hope to explore common genetic and environmental triggers in AS.
Rheumatoid Arthritis (RA)
The study looks into what causes RA. It has been found that RA-related autoantibodies exist years before the disease and that a decline in smoking parallels decline in RA, pointing to the lung as the likely site of RA initiation. This study has helped show that RA autoantibodies in first degree relatives (FDRs) correlate with tender joints, CRP, and HRCT imaging demonstrating airway inflammation. Inducible sputa/BAL reveal antibodies in FDRs. In the future, we are interested in examining inducible bronchus associated lymphatic tissue (iBALT) in FDRs, characterizing cardiac disease in antibody positive subjects, initiatinga prevention trial in pre-clinical RA, and studying environmental exposures, airways disease, and RA-related autoimmunity with population-based MESA lung and MESA air cohorts.
Systemic Lupus Erythematosus (SLE)
SLE affects women in their child-bearing years and causes marked functional and psychological disability and premature mortality due to cardiac disease. True advances from genetic and environmental studies remain elusive. Currently, we have >1000 SLE subjects in a prospective data repository. Children’s Hospital Los Angeles and the Feinstein Institute for Medical Research will study the evolution of the disease through biomarkers and genetics. The Weisman Lab uncovered the role of microvascular cardiac disease (MRI findings) as a contributor to angina chest pain and possibly ischemic heart disease. In the future, we hope to discover mechanisms of possible antibody/B-cell mediated cardiac ischemia, expand pilot data on MRI findings to a wider patient population, correlate genetic risk and biomarker evolution to clinical disease, and design and implement a prevention study based on known risks.
Hand Osteoarthritis (HOA)
HOA affects a significant proportion of the population and is clinically important. This study helps us understand how the mechanisms (genetic pathways) underlying the expression of HOA have the potential to affect the course of the disease and modify treatment. In the future, we would like to expand the pool of HOA cases using databases established to study OA at other sites and collaborate for confirmatory genetic analyses with other cohorts.