* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Increased Phagocyte and Recurring Lymphocyte Gene Activity
Survey
Document related concepts
Immune system wikipedia , lookup
Drosophila melanogaster wikipedia , lookup
Adaptive immune system wikipedia , lookup
Cancer immunotherapy wikipedia , lookup
Plant disease resistance wikipedia , lookup
Complement system wikipedia , lookup
Polyclonal B cell response wikipedia , lookup
Autoimmunity wikipedia , lookup
Hygiene hypothesis wikipedia , lookup
Molecular mimicry wikipedia , lookup
Innate immune system wikipedia , lookup
Rheumatoid arthritis wikipedia , lookup
Immunosuppressive drug wikipedia , lookup
X-linked severe combined immunodeficiency wikipedia , lookup
Biochemical cascade wikipedia , lookup
Transcript
< Index 35. Kongress der DGRh und 21. Jahrestagung der ARO Hamburg, 19. - 22. September 2007 T01.20 Increased Phagocyte and Recurring Lymphocyte Gene Activity Accompany Reactivation of Rheumatoid Arthritis after Pregnancy Häupl T. 1, Østensen M. 2, Grützkau A. 3, Radbruch A. 3, Burmester GR. 1, Villiger P. 2 (1) Rheumatologie, Charité Universitätsmedizin, (2) Rheumatologie, Inselspital Bern, (3) Deutsches Rheumaforschungszentrum Objective: In rheumatoid arthritis (RA), pregnancy reduces disease activity, but is followed by an exacerbation after delivery. Immune cells of the peripheral blood are critically involved in both, pregnancy related processes of tolerance as well as exacerbation of RA. We hypothesized that transcriptome analysis of PBMC will generate a comprehensive overview of the molecular processes of RA. Methods: The transcriptome of PBMC from RA patients and healthy women (ND) during the 3. trimester and 24 weeks after pregnancy was investigated by Affymetrix HG-U133A array hybridization. Profiles were compared with reference signatures of highly purified monocytes, T-cells, B-cells, NK-cells and granulocytes of healthy donors. Functional interpretation was performed by analyzing 32 immunologically relevant KEGG pathways with 1791 genes. Results: Most differences were found in RA post partum compared to RA during pregnancy or to ND post partum. Systematic comparison with reference signatures of the highly purified cell types revealed that pregnancy in healthy women was accompanied by an increase of monocyte- and a suppression of lymphocyte-related gene activity which both reflected predominantly changes of cellular composition in PBMC. In RA, the elevated monocyte profile components of the pregnant state persisted after delivery and were correlated with disease activity. Scoring of cell type specific gene activity for each KEGG pathway and comparing with differential expression allowed to distinguish between activation of pathway related genes and an underlying shift in cellular composition. Thus, in RA post partum, a significant gene activation was found in pathways related to adhesion, migration, defense of pathogens, and cell activation including Notch-, phosphatidylinositol-, mTor-, VEGF-, Wnt-, and MAPK-signaling. Leading genes as defined by fold change for example were the cytokines IL8 and IL1β, the chemokine receptors CCR1, CCR9 and CXCR4, the adhesion molecule PECAM1 and the receptor TNFRSF17 involved in B-cell development and activation. Conclusion: The decrease of lymphocyte-related gene activity in PBMC is a prominent finding in pregnancy that could explain antigen specific tolerance and reduced RA disease activity. After delivery, multiple cellular and molecular systems are changing in RA. Phagocyte related innate immune functions contribute in a dominant way but are obviously dependent on a recurrence of the adaptive immune system. Reflecting alertness and preparedness of immune cells in the circulation for migration into inflamed tissue sites, this complex response pattern also suggests that especially processes related to the interaction between both arms of the immune system are critical in RA disease flare.