#ECTRIMS2016 – Inflammatory Profiles of Brain Seen to Predict MS Disability

Immune activity in brain membranes may be the key to determining inflammatory profiles in the brain. These profiles, in turn, are linked to levels of brain gray matter damage, and to disability, in both early and later stages of multiple sclerosis (MS).

Researchers behind the study, which was presented during the Parallel Session 4 at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2016 Congress, underway in London through Sept. 17, showed that the findings can be used to better predict disability progression, as this is tightly linked to damage in the brain’s gray matter.

The study, “Advanced characterization of intrathecal inflammation and cortical pathology stratify early MS patients,” presented by Roberta Magliozzi, was a collaboration between researchers from the University of Verona and Imperial College London, as well as other Italian and U.K. institutions.

Researchers employed several techniques to study the relationship between immune activation in the brain and gray matter damage. Earlier research has suggested that infiltration of immune cells into the brain membranes, or meninges, is the main source of inflammation driving brain damage.

First, the team measured the levels of 68 immune mediators, called cytokines and chemokines, in the membranes and the cerebrospinal fluid of 20 deceased patients with secondary progressive MS (SPMS) and in 10 control individuals. Researchers then compared the results to analyses of cerebrospinal fluid of 70 MS patients in earlier disease stages.

In patients who had died with SPMS, the team found that the presence of certain factors (namely CXCL13, CXCL9, TNF, IFN-γ, LT-α, LT-β, IL10, IL16, IL12p40) combined to form profiles that could be linked to higher levels of inflammation and demyelination in the gray matter. These findings supported the view that inflammation first appeared in the membranes and then spread to the cerebrospinal fluid.

Similar inflammatory profiles were found in the cerebrospinal fluid of MS patients, and also associated with more brain damage. In MS patients with a lower gray matter lesion load, researchers identified a profile linked to increased regulatory factors (namely, type I IFNs, CCL22 and CCL25).

“Meningeal [brain membrane] immune activity plays a key role in creating specific intrathecal inflammatory profiles associated with different degrees of GM [gray matter] damage in both progressive and early MS. In particular, molecules related to B-cell immunity, lymphoid inflammation and pro-inflammatory activation appear associated with high levels of GM damage, while mediators linked to regulatory and innate immunity correlate with lower GM pathology involvement,” the team concluded in the ECTRIMS’ abstract.