Pregnancy is associated with reduced activity of multiple sclerosis (MS). However, the biological mechanisms underlying this pregnancy-related decrease in disease activity are poorly understood

Alessia di Sapio

Antonio Bertolotto

Arianna Sala

Christoph Kleinschnitz

Fabiana Marnetto

Francesca Gilli

Francesca Sperli

Ludwig Kappos

Marco Capobianco

Paola Valentino

Raffaele A. Calogero

Raija L. P. Lindberg

Simona Malucchi

PLoS ONE

English

PubMed

Pregnancy is associated with reduced activity of multiple sclerosis (MS). However, the biological mechanisms underlying this pregnancy-related decrease in disease activity are poorly understood.We conducted a genome-wide transcription analysis in peripheral blood mononuclear cells (PBMCs) from 12 women (7 MS patients and 5 healthy controls) followed during their pregnancy. Samples were obtained before, during (i.e. at the third, sixth, and ninth month of gestation) and after pregnancy. A validation of the expression profiles has been conducted by using the same samples and an independent group of 25 MS patients and 11 healthy controls. Finally, considering the total group of 32 MS patients, we compared expression profiles of patients relapsing during pregnancy (n = 6) with those of relapse-free patients (n = 26).Results showed an altered expression of 347 transcripts in non-pregnant MS patients with respect to non-pregnant healthy controls. Complementary changes in expression, occurring during pregnancy, reverted the previous imbalance particularly for seven inflammation-related transcripts, i.e. SOCS2, TNFAIP3, NR4A2, CXCR4, POLR2J, FAM49B, and STAG3L1. Longitudinal analysis showed that the overall deregulation of gene expression reverted to “normal” already within the third month of gestation, while in the post-partum gene expressions rebounded to pre-pregnancy levels. Six (18.7%) of the 32 MS patients had a relapse during pregnancy, mostly in the first trimester. The latter showed delayed expression profiles when compared to relapse-free patients: in these patients expression imbalance was reverted later in the pregnancy, i.e. at sixth month. provide basis for the development of novel therapeutic strategies

Gilli Francesca

Lindberg Raija L. P.

Valentino Paola

Marnetto Fabiana

Malucchi Simona

Sala Arianna

Capobianco Marco

di Sapio Alessia

Sperli Francesca

Kappos Ludwig

Calogero Raffaele A.

Bertolotto Antonio

Public Library of Science (PLOS)

Learning from Nature: Pregnancy Changes the Expression of Inflammation-Related Genes in Patients with Multiple Sclerosis

BACKGROUND: Pregnancy is associated with reduced activity of multiple sclerosis (MS). However, the biological mechanisms underlying this pregnancy-related decrease in disease activity are poorly understood. METHODOLOGY: We conducted a genome-wide transcription analysis in peripheral blood mononuclear cells (PBMCs) from 12 women (7 MS patients and 5 healthy controls) followed during their pregnancy. Samples were obtained before, during (i.e. at the third, sixth, and ninth month of gestation) and after pregnancy. A validation of the expression profiles has been conducted by using the same samples and an independent group of 25 MS patients and 11 healthy controls. Finally, considering the total group of 32 MS patients, we compared expression profiles of patients relapsing during pregnancy (n = 6) with those of relapse-free patients (n = 26). PRINCIPAL FINDINGS: Results showed an altered expression of 347 transcripts in non-pregnant MS patients with respect to non-pregnant healthy controls. Complementary changes in expression, occurring during pregnancy, reverted the previous imbalance particularly for seven inflammation-related transcripts, i.e. SOCS2, TNFAIP3, NR4A2, CXCR4, POLR2J, FAM49B, and STAG3L1. Longitudinal analysis showed that the overall deregulation of gene expression reverted to "normal" already within the third month of gestation, while in the post-partum gene expressions rebounded to pre-pregnancy levels. Six (18.7%) of the 32 MS patients had a relapse during pregnancy, mostly in the first trimester. The latter showed delayed expression profiles when compared to relapse-free patients: in these patients expression imbalance was reverted later in the pregnancy, i.e. at sixth month. CONCLUSIONS: Specific changes in expression during pregnancy were associated with a decrease in disease activity assessed by occurrence of relapses during pregnancy. Findings might help in understanding the pathogenesis of MS and may provide basis for the development of novel therapeutic strategies

Raija L P Lindberg

Raffaele A Calogero

Directory of Open Access Journals

Learning from nature: pregnancy changes the expression of inflammation-related genes in patients with multiple sclerosis.

Gilli, Francesca

Lindberg, Raija L. P.

Valentino, Paola

Marnetto, Fabiana

Malucchi, Simona

Sala, Arianna

Capobianco, Marco

di Sapio, Alessia

Sperli, Francesca

Kappos, Ludwig

Calogero, Raffaele A.

Bertolotto, Antonio

edoc

Learning from nature: pregnancy changes the expression of inflammation-related genes in patients with multiple sclerosis

Crossref

A comparison of normalization methods for high density oligonucleotide array data based on variance and bias.

A crossstudy comparison of gene expression studies for the molecular classification of lung cancer.

A gene atlas of the mouse and human protein-encoding transcriptomes.

A20 inhibits NF-kappa activation by dual ubiquitin-editing functions.

A20/ TNFAIP3, a new estrogen-regulated gene that confers tamoxifen resistance in breast cancer cells.

Activity of multiple sclerosis during pregnancy and puerperium.

Amelioration of autoimmune neuroinflammation by recombinant human alpha-fetoprotein. Exp Neurol

Analysis of 17 autoimmune disease-associated variants in type 1 diabetes identifies 6q23/ TNFAIP3 as a susceptibility locus.

Bacterial transcript imaging by hybridization of total RNA to oligonucleotide arrays.

Bioconductor: open software development for computational biology and bioinformatics.

Bone Marrow is a Reservoir for CD4+CD25+ Regulatory T Cells that Traffic through CXCL12/CXCR4 Signals.

CXCL12 (SDF1alpha) suppresses ongoing experimental autoimmune encephalomyelitis by selecting antigen-specific regulatory T cells.

Decreased NURR1 gene expression in patients with Parkinson’s disease.

Diagnosis of multiple cancer types by shrunken centroids of gene expression.

Diagnostic criteria for multiple sclerosis:

Differential expression of CxCR4 receptor in early and term human placenta.

Differential regulation of central nervous system autoimmunity by T(h)1 and T(h)17 cells.

ERGDB: Estrogen Responsive Genes. Database Nucleic Acids Research 32: D533–D536.

Exploration, normalization, and summaries of high density oligonucleotide array probe level data.

Expression monitoring by hybridization to high-density oligonucleotide arrays.

Ferna ´ndez-Pe ´rez L

First-trimester trophoblast cell model gene response to hypoxia.

Hormonal influences in multiple sclerosis.

Immune modulation in multiple sclerosis treated with pregnancy hormone estriol.

Immunology of multiple sclerosis.

In: Bioconductor projects working papers.

Metaanalysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci.

Normal human pregnancy is associated with an elevation in the immune suppressive CD25+/CD4+ regulatory T-cell subset.

Orphan nuclear receptor NR4A2 expressed in T cells from multiple sclerosis mediates production of inflammatory cytokines.

Pregnancy and multiple sclerosis (the PRIMS study): clinical predictors of post-partum relapse.

Pregnancy-induced expansion of regulatory T-lymphocites may mediate protection to multiple sclerosis activity.

Rank products: a simple, yet powerful, new method to detect differentially regulated genes in replicated microarray experiments.

Regulation of the T cell response. Clin Exp All

Sex hormones and other pregnancy-related factors with therapeutic potential in multiple sclerosis. In: Multiple Sclerosis therapeutics.

Stromal Cell-Derived Factor 1, a novel target of estrogen receptor action, mediates the mitogenic effects of estradiol in ovarian and breast cancer cells.

T cell gene expression profiling identifies distinct subgroups of Japanese multiple sclerosis patients.

Th1/Th2 cytokine patterns and clinical profiles during and after pregnancy in women with multiple sclerosis.

The analysis of CIS, SOCS1, SOCS2 and SOCS3 transcript levels in peripheral blood mononuclear cells of systemic lupus erythematosus and rheumatoid arthritis patients.

Treatment of multiple sclerosis with pregnancy hormone estriol.

Ulcerative colitis and Chron’s disease: distinctive gene expression profiles and novel susceptibility candidate genes.

Variations in chemokine receptor and cytokine expression during pregnancy in multiple sclerosis patients.

Western versus Asian types of multiple sclerosis: immunogenetically and clinically distinct disorders.

Learning from Nature: Pregnancy Changes the Expression of Inflammation-Related Genes in Patients with Multiple Sclerosis

Abstract

Similar works

Full text

Available Versions

Public Library of Science (PLOS)

Directory of Open Access Journals

edoc

Crossref