Author Of 2 Presentations
P0039 - Circulating microRNAs as potential inflammatory biomarkers of acute exacerbation in relapsing-remitting multiple sclerosis (ID 938)
Abstract
Background
Multiple sclerosis (MS) is a chronic immune-mediated inflammatory-degenerative disease of the central nervous system. MicroRNAs (miRNAs) are short sequences of 19-25 non-coding single-stranded RNA nucleotides that regulate transcriptional gene expression by inhibiting the translation of specific messenger RNA targets and protein expression respectively. miRNAs are involved in various physiological and pathological processes, in particular contribute to the activation of the Th1 and Th17 pathways that regulate the immune response. Many studies show that the miRNAs are involved in MS epigenetic mechanisms affecting both the expression of inflammatory cells and myelination factors.
Objectives
This study aimed to compare the serum miRNAs in relapsing MS patients compared to remitting ones and to healthy controls for better understanding of MS pathogenesis.
Methods
We evaluated 3 groups of subjects: 16 relapsing-remitting (RR)MS patients in relapse (Group I); 12 RRMS patients in remission (Group II) and 12 sex- and age-matched healthy controls (Group III). Total extraction of RNA from sera was performed with a column-based method that includes small RNAs and minimizes the carryover of enzyme inhibitors typically contained in biofluids (miRNEeasy serum/plasma kit, QIAGEN). Total RNA was labeled and hybridized with Human miRNA Microarray Release 21 (Agilent) containing probes for 2549 human microRNAs from the Sanger database. Arrays were verified for quality control and extracted by Agilent Feature Extraction 10.7.3.1 software and entirely processed by MATLAB (The MathWorks Inc.) in house-built routines. Deregulated miRNAs were established by permutation test and a false discovery procedure used for multiple comparisons. Unsupervised hierarchical clustering was performed to individuate specific pattern of expression among samples and clusters of miRNAs. The results obtained were validated by Real-Time PCR.
Results
We analyzed 2549 miRNA that were expressed in at least 50% of the samples. After eliminating 10 samples that expressed only a few of these miRNAs, we found 66 expressed miRNAs in the half of remained samples. Microarray analysis identified a signature of 8 deregulated miRNAs in relapsing MS patients compared to controls and remitting MS patients. In particular, among these eight miRNAs, two were up-regulated (miR-2861 and miR-6821-5p) while six were down-regulated (miR-4281, miR-5196-5p, miR-6076, miR-642a -3p, miR-671-5p, miR-6879-5p).
Conclusions
We have found several upregulated or downregulated miRNA to be correlated with disease exacerbation in RRMS patients. Previous studies have reported five of these miRNAs to be involved in other inflammatory disorders. We hypothesize that the miRNA could be useful biomarkers not only to improve diagnosis and disease control, but also to predict the phase of acute exacerbation in MS.
P0166 - Sociodemographic features and disability in African-American and Caucasian patients with Multiple Sclerosis (ID 1282)
Abstract
Background
A more severe disease course has been reported in African-American (AA) in comparison with Caucasian (CA) MS patients. Sociodemographic differences and limited access to treatment have been often used to explain the different disability profile in the two groups. To date, an objective assessment of disability in AA and potential differences with CA patients is still lacking.
Objectives
Here, we characterized sociodemographic, motor and neuropsychological features of AA and CA patients with multiple sclerosis.
Methods
Fifty-seven AA patients (43F, mean age 37.84 ± 10.54 yrs, mean disease duration 5.64 ± 5.74 yrs, median EDSS 2, EDSS range 0-6.5), 37 AA healthy controls (HC) (25F, mean age 35.97 ± 12.44 yrs), 50 CA patients (36F, mean age 39.02 ± 10.83 yrs, mean disease duration 5.90 ± 5.94 yrs, median EDSS 1.5, EDSS range 0-6) and 28 CA HC (17F, mean age 35.57 ± 11.77 yrs) were prospectively enrolled. In all subjects, an extensive neuropsychological and sensory-motor evaluation was performed. The sensory-motor evaluation included 9-hole peg test (9-HPT), grooved pegboard test (GPT), finger tapping test (FTT), 25-foot walk test (25-FWT), 2-minutes walk test (2-MWT), evaluation of segmental strength, grip strength, vibration sensitivity (VS) and standing balance (theta score from NIH toolbox). The neuropsychological evaluation included Symbol Digit Modalities Test (SDMT), California Verbal Learning Test-II (CVLT), Brief Visuospatial Memory Test–Revised (BVMT), Stroop Color and Word Test (SCVT), Controlled Oral Word Association Test (COWAT) and a multitasking attention-memory test (MAMT). Each patient’s group was compared with a race-matched HC group via ANCOVA analysis, accounting for age, gender, years of education and socioeconomic status expressed as yearly income (9 categories with 1 = less than $5,000 and 9 = $100,000+). In the comparison of cognitive performance, years of education, premorbid intelligence estimated with the Wechsler Test of Adult Reading (WTAR) and depressive symptoms evaluated via Beck Inventory were also included as covariates of no interest.
Results
AA and CA patients did not differ in age, gender, disease duration, while they did differ in total years of education (p<0.001) and yearly income (p=0.001). When compared to their matched HC group, AA and CA patients showed similar deficits in information processing speed, ambulation, manual dexterity, sensitivity and balance (p ranging from 0.029 to <0.001). While CA showed an additional impairment of verbal memory (p=0.009), AA patients showed additional involvement of verbal fluency (p=0.005), multitasking capability (p=0.024), motor speed and coordination (p=0.048) and grip strenght (p=0.041).
Conclusions
Even when accounting for sociodemographic features, AA patients show more severe and widespread disability than CA patients with MS.