Rheumatoid Arthritis Research
NYU Langone’s Division of Rheumatology actively pursues research on rheumatoid arthritis. Researchers carry out much of our clinical research at NYC Health + Hospitals/Bellevue arthritis clinic and NYU Langone Orthopedic Hospital arthritis clinic, housed at NYU Langone Ambulatory Care—23rd Street. Valuable data for our Specimen and Matched Phenotype Linked Evaluation (SAMPLE) registry also come from these locations. In addition to clinical trials, we conduct basic and translational research.
Elimination of B Cell–Produced Antibodies
Gregg Silverman, MD, in collaboration with scientists at several other institutions, has found that existing treatments for rheumatoid arthritis do little to address the underlying immunologic defect of self-attacking autoantibodies.
In their research, Dr. Silverman and colleagues analyzed memory B cells, which secrete anti-citrullinated protein antibodies (ACPAs). After developing a sensitive enzyme-linked immunosorbent assay and multiplex bead–based immunoassay to detect the presence of autoantibodies, the research team stimulated memory B cells in a cell culture system and analyzed antibodies produced by the cells. In blood samples of patients with rheumatoid arthritis with ACPAs, the team found high levels of ACPA-secreting memory B cells. In contrast, patients who lacked these autoantibodies and healthy volunteers had normal levels of memory B cells.
However, in patients whose rheumatoid arthritis had been driven into remission by methotrexate or a tumor necrosis factor inhibitor, researchers found that ACPA levels were still directly proportional to the recirculating memory B cells in the bloodstream. The patients’ clinical remission had little or no effect on the circulating burden of these ACPA-expressing B cells. This result suggests that neither drug regimen affects the underlying dysregulation of humoral immunity.
The study findings may also explain why stopping standard rheumatoid arthritis therapy even after an apparent improvement in inflammation symptoms most often results in disease reactivation and a clinical flare. The researchers concluded that a clinical disease activity score is not a reliable indicator of whether pathologic recirculating B-cell autoimmunity has been truly resolved.
Programmed Cell Death-1 Protein in Rheumatoid Arthritis
Sabina Sandigursky, MD, is investigating T-cell signaling and the programmed cell death-1 (PD-1) protein. Inhibitors of the PD-1 receptor have demonstrated their effectiveness in achieving remission in multiple cancers. The same approach could be valuable in autoimmune disease with an agonist drug.
In addition to assessing the signaling lymphocyte activation molecule–associated protein, which belongs to a family of cell surface receptors and may play a role in the function and signaling pathway of PD-1, the laboratory is evaluating how PD-1 is regulated in patients with rheumatoid arthritis. Theoretically, T cells in the synovial fluid of inflamed joints may have elevated PD-1 levels, whereas levels are lower in cellular compartments with less inflammation, such as the peripheral blood. Ultimately, this research could yield new information about how to manipulate the signaling pathway to regulate the levels and activity of PD-1.
Comorbidities and Rheumatoid Arthritis Outcomes
Our division researchers were part of a team that found patients with rheumatoid arthritis who take certolizumab pegol, and who also have depression or fibromyalgia or receive medications for depression, anxiety, or neuropathic pain, are more likely to have a poorer response to rheumatoid arthritis treatment than those without these comorbid conditions. The comorbidities group also experienced more adverse events.
Use of Biologics in Minority Populations
In line with our interest in treatment disparities, our division was also part of a research team that found that ethnic minorities in the Veterans Health Administration system received biologic agents to manage their rheumatoid arthritis at a rate similar to that of white patients. In comparison, the rate of biologics use among minority patients within the Ethnic Minority Rheumatoid Arthritis Consortium was lower than that of whites.
For more information about our rheumatoid arthritis research program, please contact firstname.lastname@example.org.