In recent years, Steere has pioneered studies of the role of infectious agents in triggering autoimmune diseases, particularly in patients with post-infectious, antibiotic-refractory Lyme arthritis or rheumatoid arthritis. The inflammation of the synovial membrane in affected joints, which is the target of an untoward immune response, is similar in both diseases. Using a novel approach of proteomics and translational research, developed with Catherine Costello at Boston University, he and his colleagues have identified four novel autoantigens that are targets of immune responses in patients with post-infectious Lyme arthritis. He has developed an algorithm for the treatment of such patients: after oral and intravenous antibiotic therapy, they are given immunosuppressive medications, such as methotrexate or TNF inhibitors, as in rheumatoid arthritis.