Rheumatoid arthritis is the most common form of chronic inflammatory arthritis, affecting approximately 1 in 100 people. Lyme disease is the most common vector-borne infection in the United States, and arthritis is the most frequent late manifestation of the infection. Despite appropriate antibiotic therapy, a small percentage of these patients have persistent arthritis, termed antibiotic-refractory Lyme arthritis. In both diseases, it is thought that the immune system reacts against self-components (autoantigens) in affected tissue in the joint (called synovial tissue), but the identity of disease-causing autoantigens is not known in either illness.
In this grant proposal, we will attempt to identify autoantigens in patients’ synovial tissue using newly developed technology. First, improvements in mass spectrometry and the development of large computer databases, which contain sequences for most of the human genome and a number of microbial genomes, now make it possible to identify peptides presented by the immune system in patients’ synovial tissue and the proteins of origin of these peptides. Second, large protein arrays, expressing over 38,000 human cloned genes, now make it possible to identify autoantibodies to human proteins in patients’ serum and/or joint fluid. If new candidate autoantigens are identified, large panels of samples from patients with rheumatoid arthritis or antibiotic-refractory Lyme arthritis will be used to determine whether these responses are commonly found in patients with these diseases.
The identification of relevant autoantigens in rheumatoid arthritis and antibiotic-refractory Lyme arthritis would be likely to have a marked impact on the diagnosis and treatment of these diseases.