Polymyalgia Rheumatica (PMR)
Conditions
Brief summary
Polymyalgia Rheumatica (PMR) is treated with corticosteroids; however, long-term treatment is not feasible due to side effects. Withdrawal of corticosteroids causes a subset of patients to relapse, and there is no current way to understand what underlies this. Our research team has preliminary data from a small clinical study that indicates that different immune effector dynamics during the tapering of steroids correlate with relapse. This was achieved using the DNA methylation-specific immune cell profiling methods that Dr. Christensen has pioneered. What is proposed is a larger prospective study of 50 PMR patients to validate differences in CD4 and CD8 memory cells as a predictor of relapse. Finally, we also focus on the Glucocorticoid Methylation Index (GCMI), which is a collection of 28 CpG islands that are methylated in response to corticosteroids. This will allow our team to determine the predictive power of the GCMI for PMR.
Interventions
None listed
Sponsors
Dartmouth-Hitchcock Medical Center
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
50 Years to 89 Years
Healthy volunteers
Yes
Inclusion criteria
Anyone ≥50-89 years old Taking ≥10mg of prednisone or prednisone equivalent at time of enrollment with a stable disease normal ESR and CRP (inflammation markers) which would indicate presence of inflammation or not * CRP: \<1.0 mg/dL (some labs report in mg/L → normal is usually \<3 mg/L) * ESR: * Men ≥50 years: 0-20 mm/hr * Women ≥50 years: 0-30 mm/hr Have a PMR diagnosis Able to provide written consent
Exclusion criteria
* History of concomitant Giant cell arteritis (GCA) any other rheumatological disorders like lupus, arthritis (psoriatic, osteo), scleroderma, sjogrens Active malignancy- presence of tumor by imaging or labs Infection- infection can cause increased levels of innate immune cells making it difficult to differentiate between disease and infection recent surgery- within the past 6 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Understanding what the exact triggers for immune activation, the specific antigens involved, and the mechanisms underlying disease relapses and glucocorticoid resistance | 12 months | DNA methylation cytometry is a novel DNA-based cell typing technology that can quantify changes in blood immune cells. The methylation cytometry approach allows for an in-depth insight into 12 immune cell populations (and over 50 immune profile variables) that is not feasible with standard clinical labs. It is both far more affordable and less labor-intensive than flow cytometry, as well as much less logistically complex because it is DNA-based and does not require intact cell membranes.14 Blood can be collected as part of the standard-of-care draw and immediately frozen for later use. DNA methylation analysis is a novel approach to understanding the immunologic underpinnings of PMR pathogenesis and treatment. |
Contacts
CONTACTVivekanand Tiwai, MD
CONTACTOlivia Brooker, BS
Outcome results
None listed