The monocyte transcriptome during pregnancy in multiple sclerosis: prominent expression of the Fc-receptor CD64

Mult Scler. 2011 Apr;17(4):389-96. doi: 10.1177/1352458510389628. Epub 2010 Dec 6.

Abstract

Background: During the third trimester of pregnancy multiple sclerosis (MS) disease activity is reduced. It is not fully understood which factors mediate this disease amelioration.

Objective: To study alterations of the monocyte transcriptome during pregnancy in MS patients, using a genomewide approach to identify differentially regulated genes.

Methods: Women with MS and healthy controls were longitudinally studied, including a visit before pregnancy.

Results: RNA-microarray analysis was performed in six patients. We found a significant increase of CD64 (Fc gamma receptor 1a, FcgR1a) during the third trimester compared with baseline, confirmed by RT-PCR in a group of ten patients. Analysis with Ingenuity software was performed using all genes expression of which was altered at least 1.5-fold in at least five out of six patients. Major networks that were altered during MS pregnancy were: cell-to-cell signalling and interaction, immune response, and cell signalling. From the genes selected for Ingenuity analysis, seven additional candidate genes, selected for their biological interest, were tested using RT-PCR in ten patients with MS and nine controls. We found an increased expression of JAK2 and STAT1 directly postpartum in patients with MS and in controls.

Conclusion: The increased CD64 expression during pregnancy is indicative of enhanced innate immune functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Gene Expression Profiling
  • Humans
  • Janus Kinase 2 / genetics
  • Janus Kinase 2 / metabolism
  • Longitudinal Studies
  • Monocytes / immunology*
  • Monocytes / metabolism
  • Multiple Sclerosis / genetics*
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / metabolism
  • Pregnancy
  • Pregnancy Complications / genetics*
  • Pregnancy Complications / immunology
  • Pregnancy Complications / metabolism
  • Pregnancy Trimester, Third / genetics
  • Pregnancy Trimester, Third / immunology
  • Pregnancy Trimester, Third / metabolism
  • Receptors, IgG / genetics*
  • Receptors, IgG / immunology
  • Receptors, IgG / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT1 Transcription Factor / genetics
  • STAT1 Transcription Factor / metabolism
  • Severity of Illness Index

Substances

  • Receptors, IgG
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Janus Kinase 2