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Researchers identified a monocyte/dendritic cell response to EBV reactivation in B cells as one of the earliest events in developing MS relapse.

A Boston-based group of scientists found a pro-inflammatory transcriptional signature in patients with MS, up to 3 months before relapse. They identified a monocyte/dendritic cell response to Epstein-Barr virus (EBV) reactivation in B cells as one of the earliest events in developing MS relapse.

Devin King, Brigham and Women’s Hospital, Massachusetts, and colleagues set out to catalog peripheral immune cells during a relapse, establish a timeline of transcriptomic mechanisms before a relapse, and identify and validate novel blood-based biomarkers of relapse¹. They presented a time-resolved single-cell atlas of the peripheral immune cells in MS relapse. This was based on single-cell RNA sequencing (scRNA-seq) of 30 clinical blood samples from 15 patients with MS and 21 age- and sex-matched healthy controls. The specimens were drawn within 90 days before relapse or during relapse and paired with remission samples. “Ultimately, we generated 42 scRNA seq-libraries, as well as 36 whole-genome sequencing (WGS) libraries, to better understand the genetic risk factors for MS,” said Dr. King. The researchers expanded this to 71 more patients with MS and generated CD3-, CD14-, and CD19-positive cell populations.

From the 15 patients with MS, Dr. King and colleagues generated a single-cell reference of 302,874 cells. Peripheral immune cells were found to exhibit widespread transcriptomic perturbations from 7 to 90 days before relapse. The strongest perturbations were found in naive B cells and intermediate B cells, followed by mucosal-associated invariant T (MAIT) and CD16 monocytes. “Interestingly, these cell perturbations have dampened considerably within 7 days after a relapse,” Dr. King added.

A pathway analysis highlighted a unified set of viral processes that precede relapse: responses to the virus, regulation of viral processes, and regulation of viral genome replication. The pre-relapse immune signature was consistent with a host-cell response to EBV activity, including both latent and lytic programs.

Dr. King said the multi-omic cellular atlas offers a wealth of new blood-based biomarkers predictive of disease activity. Several pre-relapse mechanisms are potentially targetable with new and existing therapies. This could contribute to more specific, personalized treatments for patients with MS.

Medical writing support was provided by Michiel Tent.
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