The research activities of the Section of Rheumatology extend from laboratory based basic science investigations to patient care initiatives aimed at improving diagnosis and treatment. Our research laboratories enjoy excellent support from federal agencies (such as the National Institutes of Health) and private foundations (such as the Arthritis Foundation). The success of our research derives from strong interactions and collaborations with other entities at The University of Chicago interested in the prevention and treatment of autoimmune diseases. All basic researchers in the Section of Rheumatology are members of the Committee on Immunology, an interactive group that comprises all faculty members of The University of Chicago with a research interest in Immunology. The Committee on Immunology includes world-renowned lymphocyte experts, including Albert Bendelac, the Committee’s chairman, Harinder Singh and Ursula Storb. In addition, the basic researchers of the Section of Rheumatology have strong ties with The University of Chicago Knapp Center for Lupus and Immunology Research, a research center lead by the member of the National Academy of Sciences, Martin Weigert, a leader in the field of B cell biology.
Clinical research activities of the section include the testing of diagnostic methods and therapeutic agents developed either at The University of Chicago or under outside auspices such as pharmaceutical manufacturers or colleagues in the academic community nationwide. Current and recent testing of therapies developed at The University of Chicago includes studies aimed at modifying the course of disease such as rheumatoid arthritis, psoriatic arthritis and scleroderma. Patients are also involved in studies on systemic lupus, osteoarthritis, gout, and inflammatory muscle disease.
The basic research in the Section of Rheumatology focuses on the biology of T and B lymphocytes. Lymphocytes are essential for the elimination of microbial pathogens and tumors, but are also responsible for the development of autoimmune diseases and the rejection of transplanted organs. Understanding how T and B lymphocytes develop and become activated is important to create the new generation of immunosuppressive agents that target selective lymphocytes responsible for disease.
The basic research team comprises Marcus Clark, M.D., Chief of the Section of Rheumatology and Professor of Medicine, Maria-Luisa Alegre, M.D., Ph.D., Professor of Medicine, Fotini Gounari, Ph.D., Associate Professor of Medicine, and Patrick Wilson, Ph.D., Professor of Medicine.
Clinical research studies have been undertaken in the Section of Rheumatology at The University of Chicago for more than three decades. The primary aims of clinical research program in the Rheumatology Section are to advance knowledge in specific diagnostic and therapeutic areas of clinical science and to expedite the delivery of advances in basic biological and social sciences to patient care. Through basic and clinical research insights achieved by Section faculty and faculty colleagues at The University of Chicago, the Rheumatology Section has frequently been able to offer its patients early access to novel diagnostic and therapeutic advances in important areas of contemporary rheumatologic science. The section faculty has also participated in multi-center cooperative analyses aimed at achieving a more sophisticated understanding of the courses, manifestations, and management of a number of important rheumatic diseases. In addition, the Section has actively pursued studies (often under the sponsorship of the National Institutes of Health and/or pharmaceutical and bio-technology companies) of promising diagnostic modalities and of new pharmaceutical and biological agents in the treatment of major arthritic and immunologic diseases.
Exciting research is being conducted within the Section of Rheumatology, where basic and clinical investigators are working very hard to develop therapeutic options to treat COVID- 19.
Dr. Wilson has three ongoing but interrelated projects:
1) Production of monoclonal antibodies from the isolated B cells of patients recovered from COVID-19. The antibodies will be developed as therapeutics, used for improved diagnostics, and the epitopes targeted and mechanisms of viral control will guide vaccine and therapeutic development.
2) Characterization of patient immune recovery and “super-responder” antibody responses in the context of the University of Chicago convalescent serum transfer therapy trial. Led by Dr. Lucia Madariaga, the University of Chicago will treat COVID-19 patients with serum from recovered blood donors. Dr. Wilson and team will characterize the donor serum and, from the PBMC fraction of the donated blood, the monoclonal antibodies that mediate successful serum transfer therapy. We will also characterize the serum and B cell response of treated serum recipient patients.
3) With epidemiologist Sarah Cobery and economist Michael Greensport and colleagues, we will perform a community wide analysis of serum antibody levels for 10,000 subjects in the Chicago area. The results of this effort will guide predictions of community immunity and drive public policy decisions. We are also in communication with the Illinois Governor’s office regarding the progress of this important effort.
1- COVIDOSE: Open label, phase 2 clinical trial to establish proof of concept that low-dose tocilizumab is effective in decreasing signs, symptoms, and laboratory evidence of COVID-19 pneumonitis in hospitalized, non-critically ill patients with clinical risk factors for clinical decompensation, intensive care utilization, and death, as determined by the clinical outcome of resolution of fever and the biochemical outcome measures of time to CRP normalization for the individual patient and the rate of patients whose CRP normalize.
2- Retrospective COVID19 patient analysis to generally better-understand the clinical syndrome and disease course of COVID-19, identify various correlates of disease progression to critical care utilization, and assess the relationship between these these trends in clinical and biochemical parameters with that of disease progression to critical care utilization and response to medications believed to have efficacy in the treatment of COVID-19.
Reem Jan,MD, Iazsmin Ventura,MD, and Patrick Onkka,MD:
This trial involves a novel dosing regimen, in which COVID-19 positive patients with risk factors for developing severe manifestations receive high-doses of hydroxychloroquine. This study will examine the tolerability of this high-dose regimen in patients that test positive for COVID-19 over a period of several days and evaluate its efficacy in decreasing symptoms and preventing hospitalization.
Kim Trotter,MD and Laarni Quimson,MD:
Kimberly Trotter and Laarni Quimson are co-investigators on the Leflunomide for the treatment of ambulatory patients with mild COVID-19 with J. Michael Millis as the principal investigator. This is a single arm and single center tolerability study of leflunomide in adult participants with mild COVID-19 being managed in the outpatient setting. The objectives are to establish proof of concept that leflunomide is well tolerated, effective in avoiding hospitalization, and effective in ameliorating mild COVID-19 symptoms including fevers.
Vladimir Liarski,MD and Iazsmin Ventura,MD:
This project is to identify risk factors for infections, hospitalization, and deaths among the community of patients that the University of Chicago serves. The initial study will be a retrospective review aimed at identifying correlations between demographic characteristics, particularly race, and outcomes. This work is in collaboration Dr. A. Adegunsoye from Pulmonary and Critical Care.
Dr. Liarski is working on statistical and machine learning models to understand the relationships between laboratory values, clinical metrics and subsequent hospital course. Also a retrospective cohort study of 4500 patients of whom 785 were positive for COVID looking at overall mortality, hospitalization rates, and death during hospital stay.
Kim Trotter,MD, Cuoghi Edens,MD and Kichul Ko,MD :
COVID-19 physician survey. Survey of adult rheumatologists perceptions of risk factors and potential outcomes in patients with rheumatic diseases during the COVID-19 pandemic. Secondary aims include evaluating how rheumatologists may have changed their clinical practices during COVID-19 pandemic, medication recommendations, and impact on fellowship education.
Iazsmin Ventura, MD and Cuoghi Edens,MD:
Enrollment of rheumatology patients diagnosed with COVID-19 in a secure, de-identified, international case reporting registry. It is our hope that the information collected will help guide rheumatologists in assessing and treating patients with rheumatologic disease and in evaluating the risk of infection and clinical outcomes in patients on immunosuppression.