RNA clue to MS disease course

By Eleanor McDermid, Senior medwireNews Reporter

Researchers say that the RNA profiles of peripheral blood mononuclear cells (PBMCs) can identify two distinct subsets of patients with multiple sclerosis (MS).

"Stratifying MS subjects into meaningful subsets in this manner has potential for personalizing patient care and for enhancing our understanding of this disease," say Philip De Jager (Brigham and Women's Hospital, Boston, Massachusetts, USA) and colleagues.

The researchers ascertained the two RNA profiles using PBMCs from 141 untreated patients in the early phase of MS. Although they had no long-term data on the untreated patients, De Jager et al also assessed the profiles in 94 patients treated with glatiramer acetate and 128 receiving interferon (IFN)-β.

In the treated patients, over about 6 years of follow up, patients with the "B" RNA profile were 40% more likely to have a relapse (clinical relapse, new lesions on imaging, or worsening disability), than were patients with the "A" profile. This association was independent of age and gender. It remained significant among patients treated with glatiramer acetate and there was a trend in that direction among those receiving IFN-β.

The researchers believe that they "may have uncovered information relating to the pathophysiology of MS," and that patients with the A profile may benefit from early aggressive treatment.

Notably, the A and B RNA profiles were unaltered in the treated relative to the untreated patients, "suggesting that the underlying architecture of the disease may not be fundamentally altered by these two treatments," writes the team in Science Translational Medicine.

The two RNA profiles were distinguished by differential expression of 98 probe sets, which mainly related to adaptive immune functions. For example, patients with the A profile had higher expression of genes involved in T-cell and B-cell receptor pathways, as well as increased expression of genes in the nuclear factor of activated T cells, phosphatidylinositol 3-kinase, and epidermal growth factor signaling pathways.

This suggests that patients with the A profile have either more lymphocytes or more activated lymphocytes in their blood than those with the B profile, says the team.

"Our study is an important step towards the goal of personalized medicine in MS, but much work remains to be done to understand under which circumstance and in combination with which other information this transcriptional signature may become useful in a clinical setting," said De Jager in a press statement.

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