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


CONCLUSIONS
The increased CD64 expression during pregnancy is indicative of enhanced innate immune functions.
Department of Neurology, Erasmus MC, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Rinze F
RF
Neuteboom
Evert
E
Verbraak
Annet F
AF
Wierenga-Wolf
Jane S A
JS
Voerman
Marjan van
Mv
Meurs
Sigrid M
SM
Swagemakers
Peter J
PJ
van de Spek
Eric A P
EA
Steegers
Christianne J M
CJ
de Groot
Jon D
JD
Laman
Rogier Q
RQ
Hintzen
D000328:Adult; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism; D008137:Longitudinal Studies; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D011263:Pregnancy Trimester, Third / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017452:Receptors, IgG / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D012720:Severity of Illness Index
D017452:Receptors, IgG; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D053614:Janus Kinase 2