Interaction between rheumatoid arthritis and pregnancy: correlation of molecular data with clinical disease activity measures.
OBJECTIVE
The factors that induce remission of RA during pregnancy and the relapse occurring after delivery remain an enigma. In a previous study, we investigated gene-expression profiles of peripheral blood mononuclear cells (PBMC) in patients with RA and healthy women in late pregnancy and postpartum. Profiles of samples from both groups were similar in late pregnancy with elevated monocyte and decreased lymphocyte signatures. Postpartum, in RA PBMC the high level of monocyte transcripts persisted. Further increase was observed in adhesion, migration and signalling processes related to monocytes but also in lymphocytes despite similar clinical activity due to intensified drug treatment. This prompted us to investigate correlations between clinical parameters of disease activity and gene profiles.


METHODS
Transcriptome data were correlated with RADAI, CRP, monocyte and lymphocyte counts. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotations, monocytes and lymphocytes signatures were used as reference information.


RESULTS
Comparative analysis of PBMC expression profiles from RA patients during and after pregnancy with RADAI and CRP revealed a correlation of these disease activity parameters predominantly with monocyte transcripts. Genes related to cellular programs of adhesion, migration and response to infections were upregulated. Comparing clinically active and not-active RA patients postpartum revealed a cluster of 19 genes that could also identify active disease during pregnancy.


CONCLUSIONS
The data suggest that an increase of the RADAI and an elevation of CRP is a consequence of molecular activation of monocytes. Furthermore, they indicate that molecular activation of T lymphocytes may remain clinically unrecognized postpartum. It is conceivable that a set of 19 genes may qualify as molecular disease activity marker.
Häupl
T
T
Department of Rheumatology and Clinical Immunology, Charité-University Medicine, Tucholskystr. 2, 10117 Berlin, Germany. thomas.haeupl@charite.de
Østensen
M
M
Grützkau
A
A
Burmester
G-R
GR
Villiger
P M
PM
D000208:Acute Disease; D000328:Adult; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D049590:Postpartum Period / Q000235:genetics / Q000276:immunology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics / Q000276:immunology*; D011263:Pregnancy Trimester, Third; D018709:Statistics, Nonparametric; D055815:Young Adult
D015415:Biomarkers; D002097:C-Reactive Protein