RT Journal Article
SR Electronic
T1 Monocyte alterations in rheumatoid arthritis are dominated by preterm release from bone marrow and prominent triggering in the joint
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP annrheumdis-2017-211649
DO 10.1136/annrheumdis-2017-211649
A1 Biljana Smiljanovic
A1 Anna Radzikowska
A1 Ewa Kuca-Warnawin
A1 Weronika Kurowska
A1 Joachim R Grün
A1 Bruno Stuhlmüller
A1 Marc Bonin
A1 Ursula Schulte-Wrede
A1 Till Sörensen
A1 Chieko Kyogoku
A1 Anne Bruns
A1 Sandra Hermann
A1 Sarah Ohrndorf
A1 Karlfried Aupperle
A1 Marina Backhaus
A1 Gerd R Burmester
A1 Andreas Radbruch
A1 Andreas Grützkau
A1 Wlodzimierz Maslinski
A1 Thomas Häupl
YR 2017
UL http://ard.bmj.com/content/early/2017/11/30/annrheumdis-2017-211649.abstract
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.