Scientists have identified two distinct transcription profiles in the peripheral blood of multiple sclerosis (MS) patients that can be used to divide the disease into two separate subtypes, one of which is linked with increased disease activity. The Brigham and Women’s Hospital researchers hope their data will provide molecular insights that may aid in the design of new targeted drugs or personalized treatment regimens.
Philip De Jager, M.D., and colleagues carried out transcription profiling of peripheral blood mononuclear cells (PBMCs) from 141 untreated MS patients, and also from two separate cohorts of patients receiving either of the two first-line disease-modifying therapies glatiramer acetate (GA), or interferon-β (IFN-β). The results found that MS patients exhibited one of two distinct transcription profiles—designated MSA and MSB —irrespective of treatment status, and that the MSA profile was associated with higher expression of molecules involved in lymphocyte signaling pathways. This suggests that patients in the MSA group may have a greater number of lymphocytes, or more activated lymphocytes in their peripheral blood, the authors suggest. “This observation fits with our existing knowledge of MS pathophysiology in which both B and T cells play an important role in the early, inflammatory phase of MS, which was the focus of this study.” Notably, patients displaying the MSA transcription profile were more likely to have a new inflammatory event while receiving treatment with either GA or IFN-β.
Reporting their data in Science Translational Medicine, Dr. De Jager et al admit their results will need further validation in prospective cohorts. “If this validation is achieved, we speculate that it may be useful to recognize this population architecture when performing studies of MS patients, particularly as the likelihood for further inflammatory events differs in the two subsets of MS patients,” they write.
And while the classification of patients as MSA or MSB could feasibly used to predict future inflammatory events, further longitudinal studies will also be needed to see if an individual MS patient fluctuates between the MSA and MSB states, or whether they display just one of the two transcription profiles over the course of disease. Nevertheless, the authors write, “We report a transcriptional signature that distinguishes a subset of MS patients with more active disease. Stratifying MS subjects into meaningful subsets in this manner has potential for personalizing patient care and for enhancing our understanding of this disease...Whether our signature provides a surrogate marker for active, asymptomatic inflammation or captures an underlying difference in the pathophysiology of different subjects with MS, this information could be leveraged in the future to enhance patient care and drug development.”
The Brigham and Women's Hospital researchers outline their findings in a paper titled "An RNA Profile Identifies Two Subsets of Multiple Sclerosis Patients Differing in Disease Activity."