Abstract
ObjectiveWe tested the hypothesis that the expression of IL-33 in MS is dynamic and is likely to reflect the clinical and radiological changes during the course of RRMS.MethodsMS with either clinical or radiological relapses were recruited for the study and followed for one year. IL-33 and a panel of genes was measured by q PCR and flow cytometry at different time points.ResultsAmong 22 RRMS patients, 4 patients showed highest levels of IL-33 at the time they were recruited to the study (Month 0); in 14 patients highest levels of IL-33 were seen between 6–11 months after relapse and in 4 patients maximal levels of IL-33 were seen 12 months after relapse. A similar pattern of IL-33 kinetics was seen when IL-33 was measured by flow cytometry in an additional cohort of 12 patients. The timing of the improvement clinically did not correlate with IL-33 expression with highest expression levels either preceding or following clinical recovery. From our whole genome RNA-sequencing data we found a strong correlation between expression levels of IL-33 and a ~2000 mRNA genes. However, none of these genes encoded proteins involved in either innate or adaptive immunity. Rather, many of the genes that correlated highly with IL-33 encoded to proteins involved in DNA repair or mitochondrial function and mRNA splicing pathways.InterpretationGiven the neuro-reparative and remodeling functions attributed to IL-33, it is likely that some of the novel genes we have uncovered may be involved in repair and recovery of the CNS in MS.
Highlights
Onset of new clinical signs consistent with lesions of the optic nerve, spinal cord and brain stem of subcortical white matter represent common presentations of an acute clinical relapse in Multiple Sclerosis (MS) [1]
Among 22 RRMS patients, 4 patients showed highest levels of IL-33 at the time they were recruited to the study (Month 0); in 14 patients highest levels of IL-33 were seen between 6–11 months after relapse and in 4 patients maximal levels of IL-33 were seen 12 months after relapse
From our whole genome RNA-sequencing data we found a strong correlation between expression levels of IL-33 and a ~2000 mRNA genes
Summary
Onset of new clinical signs consistent with lesions of the optic nerve, spinal cord and brain stem of subcortical white matter represent common presentations of an acute clinical relapse in Multiple Sclerosis (MS) [1]. Dissemination of lesions is space and time is a requisite to make the diagnosis of clinically definite MS [2]. Patients who present with initial neurological symptoms which are typical of MS, but without additional evidence of involvement of lesions in either space or time, are referred to as having Clinically Isolated Syndrome (CIS). Relapses are associated with the development of new gadolinium enhancing lesions or new T2 lesions [3,4,5]. Inflammation in the brain is often clinically silent and presence of many new enhancing lesions is not often associated with new clinical signs or symptoms. The process of recovery is variable both within each patient in response to relapses at different times and between RRMS patients [7]
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