Better recovery in children may be linked to the activation of genes that, in turn, impair the activation of immune cells driving inflammation in MS.
The study, “Clinical and transcriptional recovery profiles in pediatric and adult multiple sclerosis patients,” was published in the journal Annals of Clinical and Translational Neurology.
Pediatric-onset MS (POMS), where the disease affects patients younger than 18 years old, comprises 2–5% of all MS cases. Compared with adult-onset MS (AOMS), POMS patients have a higher relapse rate but the disease is slower to progress.
Few studies have addressed whether POMS and AOMS patients show differences in the initial stages of disease in terms of severity and recovery, and whether these could be linked to differences in gene activity in blood cells.
To answer these questions, a group of researchers at the Sheba Medical Center, in Israel, performed a retrospective analysis of clinical data from 2,153 RRMS patients (1,500 women, mean age at onset of 27.3 years). Of these, 269 were POMS patients (mean age at onset 1of 5.6 years) and 1,884 were AOMS patients (mean age at onset of 29 years).
They analyzed data from patients after their first and second relapses, as well as after six months of recovery. Patients who received disease-modifying therapies (DMTs) between their first and second relapses were excluded from the second relapse analysis.
Of the 2,153 RRMS patients analyzed after the first relapse, 998 received DMTs and were excluded from the second relapse analysis. The remaining patients started DMTs 3.2 years after the second relapse.
When comparing POMS and AOMS patients after the first relapse, the researchers observed that relapses were more severe in POMS patients, as shown by a significantly higher mean expanded disability status scale (EDSS) score of 2.7, compared with an EDSS score of 2 in patients with AOMS. The EDSS score quantifies MS disability, with higher scores indicating greater disability.
A higher proportion of POMS patients, both men and women, had an EDSS of three or higher compared with AOMS patients. The mean EDSS was higher (mean score of 2.7) in boys with POMS than in men with AOMS (mean score of 2.3), but no differences were seen between girls with POMS and women with AOMS.
The mean EDSS score six months after the first relapse was of 1.3, with 79.2% of patients showing incomplete recovery (or residual disability, as shown by a difference of one or higher in the EDSS score between the six-month post-relapse and the pre-relapse EDSS score).
A higher proportion of AOMS patients showed incomplete recovery compared with POMS patients. Overall, an EDSS of three or higher was strongly associated with a higher proportion of patients with incomplete recovery. However, when considering AOMS and POMS patients separately, the researchers observed that a higher EDSS score at relapse was linked to poor recovery only in the AOMS patients.
“In POMS patients good recovery was observed independently from EDSS at relapse,” the researchers wrote.
The second relapse occurred significantly earlier in POMS patients (within 0.9 years of the first relapse) compared with AOMS patients (within 3.5 years).
The mean EDSS score was similar in both groups before the second relapse — 1.4 in POMS patients and 1.3 for AOMS — but the increase in mean EDSS score at the second relapse was higher for POMS, a score of 1.5 vs. 1.2 in the AOMS group.
Despite this, the proportion of patients with high disability (EDSS of three or higher) was similar between both groups (45% vs. 41%).
In addition, AOMS was associated with a higher proportion of incomplete recoveries after the second relapse. This was significant, however, only in men with AOMS.
A total of 46% of POMS and 49% of AOMS patients reported multiple disease symptoms.
The researchers then assessed whether recovery from relapses was linked to changes in gene activity in peripheral blood mononuclear cells (PBMCs). They analyzed blood samples from 15 POMS and 15 AOMS patients obtained six months after the first relapse, and compared them with samples from 55 healthy participants (46 adults, mean age of 34.4 years, and nine children, mean age of 13.9).
POMS patients who had a complete recovery following the first relapse showed changes in 19 genes, which were mainly linked to a suppression of antigen presentation — a process in which immune T-cells induce an immune reaction against these antigens.
In contrast, POMS patients who failed to recover from their first relapse showed changes in 28 genes that were mainly associated with the activation of B-cells, a type of immune cell that drives inflammation in MS and immune attacks against myelin (the protective coat on neurons that is damaged in MS).
Overall, the team concluded that while “POMS patients may have more severe first and second relapses than AOMS, … most often, POMS have better recovery.”
According to them, this is likely linked to age-related changes in genes in PBMCs that regulate the responses of T-cells and B-cells, two key players in MS.
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