title: Learning from nature: pregnancy changes the expression of inflammation-related genes in patients with multiple sclerosis.
abstract: 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.
  
  
  METHODS
  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
  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.
authors.affiliation: Regional Centre for Multiple Sclerosis and Clinical Neurobiology, Azienda Ospedaliera Universitaria San Luigi Gonzaga, Orbassano, Italy. francesca.gilli@fastwebnet.it
authors.forename: Francesca
authors.initials: F
authors.lastname: Gilli
authors.forename: Raija L P
authors.initials: RL
authors.lastname: Lindberg
authors.forename: Paola
authors.initials: P
authors.lastname: Valentino
authors.forename: Fabiana
authors.initials: F
authors.lastname: Marnetto
authors.forename: Simona
authors.initials: S
authors.lastname: Malucchi
authors.forename: Arianna
authors.initials: A
authors.lastname: Sala
authors.forename: Marco
authors.initials: M
authors.lastname: Capobianco
authors.forename: Alessia
authors.initials: A
authors.lastname: di Sapio
authors.forename: Francesca
authors.initials: F
authors.lastname: Sperli
authors.forename: Ludwig
authors.initials: L
authors.lastname: Kappos
authors.forename: Raffaele A
authors.initials: RA
authors.lastname: Calogero
authors.forename: Antonio
authors.initials: A
authors.lastname: Bertolotto
mesh_terms: D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D009103:Multiple Sclerosis / Q000235:genetics*; D011247:Pregnancy
chemical_list: D018836:Inflammation Mediators