Physician Investigator (Cl) Rheumatology Unit, Mass General Research Institute

Professor of Medicine Harvard Medical School

Physician Rheumatology Unit, Massachusetts General Hospital

MD Columbia University College of Physicians & Surgeons 1969

antibiotic refractory lyme arthritis; antibodies bacterial; arthritis infectious; b. burgdorferi; bacterial outer membrane proteins; borrelia burgdorferi; borrelia burgdorferi group; lipoproteins; lyme; lyme disease; rheumatoid arthritis; synovial membrane Dr. Steere’s main research initiatives involve studies of autoimmunity in chronic inflammatory forms of arthritis. These studies include the identification of HLA-DR-peptide epitopes in synovial tissue from patients with antibiotic-refractory Lyme arthritis or rheumatoid arthritis, the characterization of T effector and T regulatory cells in synovial fluid in patients with these diseases, and the development of diagnostic tests for Lyme disease and biomarkers of disease activity in rheumatoid arthritis. These studies are done in collaboration with the Mass Spectrometry Resource Center at Boston University School of Medicine under the direction of Dr. Catherine Costello.

Dr. Steere and his colleagues are focusing on studies of autoimmunity in human patients with antibiotic-refractory Lyme arthritis or rheumatoid arthritis. A small percentage of patients with Lyme arthritis have persistent proliferative synovitis for months or even several years after antibiotic treatment and apparent spirochetal killing. This outcome is associated with similar HLA-DR alleles as rheumatoid arthritis, particularly the HLA-DRB1*0401 and 0101 alleles. T cell epitopes of putative autoantigens are being sought using patient synovial tissue as a source of naturally expressed MHC complexes from which peptides are being eluted and identified using tandem mass spectrometry and proteomic database comparisons. B cell epitopes of putative autoantigens are being sought using patient sera to screen large arrays of expressed human proteins. Patients’ T cells are tested for reactivity with candidate autoantigenic T cell epitopes, and patients’ serum samples are tested for autoantibodies. The goal is to identify autoantigens that play a pathogenetic role in these chronic inflammatory forms of arthritis. In addition, the Steere laboratory is studying immune reactants in the joint fluid and synovial tissue of these patients. These inflammatory mediators, including chemokines and cytokines, are being characterized and correlated with clinical findings in patients. The goal is to understand better the pathogenesis of these diseases and to identify responses that may be used as biomarkers of disease activity.

In Lyme arthritis, the Steere laboratory is exploring spirochetal and host factors that lead to apparent tissue-specific, autoimmunty in the synovial tissue of patients with antibiotic-refractory arthritis. They are identifying subtypes of Borrelia burgdorferi in patients with Lyme arthritis and the characteristics of the immune response elicited by each type. In addition, they are determining HLA-DR alleles and single nucleotide polymorphisms in host immune response genes that are associated with antibiotic-refractory Lyme arthritis, as well as the functional characteristics of the immune response associated with each of these polymorphisms. In addition, the frequencies of T cells directed against particular proteins or glycolipids of Borrelia burgdorferi are being determined using tetramer reagents, and in both diseases, the numbers and function of T effector and T regulatory cells are being determined during active arthritis and as the arthritis resolves.

In rheumatoid arthritis, Dr. Steere and his colleagues are studying biomarkers of disease activity in patients with early rheumatoid arthritis, prior to DMARD therapy and after treatment with these drugs. The goal is to identify immune markers at disease onset that predict for incomplete response to therapy.

Finally, the Steere laboratory continues to work on the development of diagnostic tests for Lyme disease. This includes the use of arrays of B. burgdorferi proteins to identify candidate antigens for use in serologic tests for the infection. In addition, they are attempting to identify common responses that might decline rapidly after antibiotic treatment, which could be used for as a surrogate marker for spirochetal eradication.

Dr. Cadavid, a neurologist, and Dr. Londono, a postdoctoral fellow, are using a mouse model of Borrelia turicatae infection to determine mechanisms by which IL-10 protects the brain from internal bleeding caused by this infection.