Laboratory of Allen Steere, MD

Overview

The Steere Lab is best known for translational studies of Lyme disease, which include the development of diagnostic tests, and efforts to understand host immune and genetic factors causing disadvantageous outcomes. Currently, the studies focus on post-infectious syndromes following Lyme disease. These have shown that post-infectious, antibiotic-refractory Lyme arthritis is caused by the development of an excessive, dysregulated pro-inflammatory immune response during the infection, which persists in the post-infectious period. The consequences of this excessive response in Lyme synovial tissue include vascular damage, autoimmune and cytotoxic processes, and fibroblast proliferation and fibrosis, a synovial lesion similar with that of the other chronic inflammatory forms of arthritis, including rheumatoid arthritis. We are determining phenotypes and antigenic drivers of T and B cells responsible for these maladaptive immune responses.

In more recent years, studies of the role of infection-induced autoimmunity in Lyme arthritis led to studies of the “mucosal origins hypothesis” in rheumatoid arthritis (RA). This hypothesis posits that mucosal sites, such as the gut, are initial sites where immune responses first develop that may, months-to-years later, result in clinical RA. We are focusing on the identification of gut commensal microbes, such as Prevotella copri, which trigger autoimmune responses that appear to translocate to joints leading to clinical rheumatoid arthritis. Several hypotheses are being explored to explain this translocation. First, molecular mimicry between microbial and host T cell epitopes along with epitope spreading may be a potential link between gut microbial immunity and autoimmunity in joints. Second, the microbe itself, or components of it, may spread to joints, where they trigger autoimmune responses. As with Lyme arthritis, we are determining phenotypes and antigenic drivers of T and B cells responsible for these immune responses.

These studies are funded by two NIH-sponsored program projects, one concerning Lyme disease and the other about RA and by philanthropic support from the Philip Morse Fund. Samples for these translational studies come from patients seen in the Rheumatology Clinic at MGH and from other institutions that are participating in these program projects.

Goals

In Lyme arthritis (LA): to identify host and/or B. burgdorferi antigens and epitopes that drive the immune responses in post-infectious, antibiotic-refractory LA and to characterize that nature of these responses.

In rheumatoid arthritis (RA): to identify commensal microbial agents, antigens, and epitopes that drive immune responses in RA and to characterize the nature of these responses.

To participate in these studies with a range of investigators who have expertise in specific areas relevant to these goals, thereby increasing the likelihood of success in these projects.

To provide an exceptional experience for post-doctoral fellows and junior investigators in cutting-edge studies of chronic inflammatory forms of arthritis.

Research Projects

The projects are relevant to RA and LA

• Identification of HLA-DR peptide epitopes from microbial or self-proteins in synovial tissue and testing implicated peptides for T and B cell responses.
• Evaluation of implicated T cells for molecular mimicry between homologous microbial and self-proteins.
• Assessment of antibody cross-reactivity using recombinant microbial and self-proteins.
• Characterization of immune cells phenotypes by flow cytometry and single cell RNAseq.
• Determination of biomarkers and serologic tests for improvement in patient diagnosis and treatment.

Publications

View publications here