PT  - JOURNAL ARTICLE
AU  - Biljana Smiljanovic
AU  - Anna Radzikowska
AU  - Ewa Kuca-Warnawin
AU  - Weronika Kurowska
AU  - Joachim R Grün
AU  - Bruno Stuhlmüller
AU  - Marc Bonin
AU  - Ursula Schulte-Wrede
AU  - Till Sörensen
AU  - Chieko Kyogoku
AU  - Anne Bruns
AU  - Sandra Hermann
AU  - Sarah Ohrndorf
AU  - Karlfried Aupperle
AU  - Marina Backhaus
AU  - Gerd R Burmester
AU  - Andreas Radbruch
AU  - Andreas Grützkau
AU  - Wlodzimierz Maslinski
AU  - Thomas Häupl
TI  - Monocyte alterations in rheumatoid arthritis are dominated by preterm release from bone marrow and prominent triggering in the joint
AID  - 10.1136/annrheumdis-2017-211649
DP  - 2017 Nov 30
TA  - Annals of the Rheumatic Diseases
PG  - annrheumdis-2017-211649
4099  - http://ard.bmj.com/content/early/2017/11/30/annrheumdis-2017-211649.short
4100  - http://ard.bmj.com/content/early/2017/11/30/annrheumdis-2017-211649.full
AB  - Objective Rheumatoid arthritis (RA) accompanies infiltration and activation of monocytes in inflamed joints. We investigated dominant alterations of RA monocytes in bone marrow (BM), blood and inflamed joints.Methods CD14+ cells from BM and peripheral blood (PB) of patients with RA and osteoarthritis (OA) were profiled with GeneChip microarrays. Detailed functional analysis was performed with reference transcriptomes of BM precursors, monocyte blood subsets, monocyte activation and mobilisation. Cytometric profiling determined monocyte subsets of CD14++CD16−, CD14++CD16+ and CD14+CD16+ cells in BM, PB and synovial fluid (SF) and ELISAs quantified the release of activation markers into SF and serum.Results Investigation of genes differentially expressed between RA and OA monocytes with reference transcriptomes revealed gene patterns of early myeloid precursors in RA-BM and late myeloid precursors along with reduced terminal differentiation to CD14+CD16+monocytes in RA-PB. Patterns associated with tumor necrosis factor/lipopolysaccharide (TNF/LPS) stimulation were weak and more pronounced in RA-PB than RA-BM. Cytometric phenotyping of cells in BM, blood and SF disclosed differences related to monocyte subsets and confirmed the reduced frequency of terminally differentiated CD14+CD16+monocytes in RA-PB. Monocyte activation in SF was characterised by the predominance of CD14++CD16++CD163+HLA-DR+ cells and elevated concentrations of sCD14, sCD163 and S100P.Conclusion Patterns of less mature and less differentiated RA-BM and RA-PB monocytes suggest increased turnover with accelerated monocytopoiesis, BM egress and migration into inflamed joints. Predominant activation in the joint indicates the action of local and primary stimuli, which may also promote adaptive immune triggering through monocytes, potentially leading to new diagnostic and therapeutic strategies.