PMID- 36493973
OWN - NLM
STAT- MEDLINE
DCOM- 20221227
LR  - 20230211
IS  - 1095-953X (Electronic)
IS  - 0969-9961 (Linking)
VI  - 176
DP  - 2023 Jan
TI  - Age-related blood transcriptional regulators affect disease progression in 
      pediatric multiple sclerosis.
PG  - 105953
LID - S0969-9961(22)00345-X [pii]
LID - 10.1016/j.nbd.2022.105953 [doi]
AB  - BACKGROUND: Pediatric onset multiple sclerosis patients (POMS) are defined as 
      multiple sclerosis with an onset before the age of 18 years. Compared to adult 
      onset multiple sclerosis (AOMS), POMS has more severe disease activity at onset, 
      but better recovery. Little is known about the molecular mechanism responsible 
      for the differences in the clinical presentations. METHODS: Peripheral Blood 
      Mononuclear Cells samples were taken from 22 POMS patients (mean age 
      14.1 +/- 2.4 years, 15 females, 7 male), and 16 AOMS patients, (mean age 
      30.8 +/- 6.1 years,10 females, 6 males), and gene-expression were analyzed using 
      Affymetrix Inc. HU-133-A2 microarrays. Differentially Expressed Genes (DEGs) that 
      significantly distinguished between POMS and AOMS with pvalue <0.05 after false 
      discovery rate correction were evaluated using Partek software. Twenty-one 
      matched age and gender control was applied to clarify age-related changes. 
      Clinical assessment was performed by analysis of expanded disability status scale 
      (EDSS) and brain MRI lesion loads. Gene functional analysis was performed by 
      Ingenuity Pathway Analysis software. RESULTS: Compared to AOMS, POMS had higher 
      EDSS (3.0 IQR 2.0-3.0 and 2.0 IQR 2.0-3.0, p = 0.005), volume of T1 (2.72 mm(3), 
      IQR 0.44-8.39 mm(3) and 0.5 mm(3) IQR 0-1.29 mm(3) respectively, p = 0.04) and T2 
      (3.70 mm(3), IQR 1.3-9.6 and 0.96 mm(3), IQR 0.24-4.63 respectively, p = 0.02) 
      brain MRI lesions. The POMS transcriptional profile was characterized by 551 
      DEGs, enriched by cell cycling, B lymphocyte signaling and senescent pathways 
      (p < 0.02). Of these, 183 DEGs significantly correlated with T2 lesions volume. 
      The POMS MRI correlated DEGs (n = 183) and their upstream regulators (n = 718) 
      has overlapped with age related DEGs obtained from healthy subjects (n = 497). 
      This evaluated common DEGs (n = 29) defined as POMS age-related regulators, 
      suggesting to promote effect on disease severity. CONCLUSION: Our finding of 
      higher transcriptional levels of genes involved in cell cycle, cell migration and 
      B cell proliferation that promoted by transcriptional level of age-associated 
      genes and transcription factors allows better understanding of the more 
      aggressive clinical course that defines the POMS.
CI  - Copyright (c) 2022 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Shavit, Eitan
AU  - Shavit E
AD  - Multiple Sclerosis Center, Sheba Medical Center, Ramat-Gan, Israel; St. George's 
      Hospital Medical School, University of London, London, United Kingdom; Arrow 
      project for medical research education, Sheba Medical Center, Ramat-Gan, Israel. 
      Electronic address: EitanGershon.Shavit@sheba.health.gov.il.
FAU - Menascu, Shay
AU  - Menascu S
AD  - Multiple Sclerosis Center, Sheba Medical Center, Ramat-Gan, Israel; Sackler 
      School of Medicine, Tel-Aviv University, Tel Aviv, Israel. Electronic address: 
      Shay.Menascu@sheba.health.gov.il.
FAU - Achiron, Anat
AU  - Achiron A
AD  - Multiple Sclerosis Center, Sheba Medical Center, Ramat-Gan, Israel; Sackler 
      School of Medicine, Tel-Aviv University, Tel Aviv, Israel. Electronic address: 
      Anat.Achiron@sheba.health.gov.il.
FAU - Gurevich, Michael
AU  - Gurevich M
AD  - Multiple Sclerosis Center, Sheba Medical Center, Ramat-Gan, Israel; Sackler 
      School of Medicine, Tel-Aviv University, Tel Aviv, Israel. Electronic address: 
      Michael.Gurevich@sheba.health.gov.il.
LA  - eng
PT  - Journal Article
DEP - 20221206
PL  - United States
TA  - Neurobiol Dis
JT  - Neurobiology of disease
JID - 9500169
SB  - IM
MH  - Adult
MH  - Child
MH  - Female
MH  - Humans
MH  - Male
MH  - Adolescent
MH  - Young Adult
MH  - *Multiple Sclerosis/genetics
MH  - Leukocytes, Mononuclear
MH  - Age of Onset
MH  - Disease Progression
MH  - Magnetic Resonance Imaging
OTO - NOTNLM
OT  - Gene expression
OT  - Pediatric multiple sclerosis
OT  - Peripheral blood mononuclear cells
EDAT- 2022/12/10 06:00
MHDA- 2022/12/28 06:00
CRDT- 2022/12/09 19:35
PHST- 2022/05/19 00:00 [received]
PHST- 2022/12/04 00:00 [revised]
PHST- 2022/12/05 00:00 [accepted]
PHST- 2022/12/10 06:00 [pubmed]
PHST- 2022/12/28 06:00 [medline]
PHST- 2022/12/09 19:35 [entrez]
AID - S0969-9961(22)00345-X [pii]
AID - 10.1016/j.nbd.2022.105953 [doi]
PST - ppublish
SO  - Neurobiol Dis. 2023 Jan;176:105953. doi: 10.1016/j.nbd.2022.105953. Epub 2022 Dec 
      6.