Monocyte alterations in rheumatoid arthritis are dominated by preterm release from bone marrow and prominent triggering in the joint

Abstract

ObjectiveRheumatoid 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.MethodsCD14+ 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.ResultsInvestigation 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.ConclusionPatterns 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.

Hypogalactosylation of immunoglobulin G in rheumatoid arthritis: relationship to HLA-DRB1 shared epitope, anticitrullinated protein antibodies, rheumatoid factor, and correlation with inflammatory activity

“…Finally, association of IgG hypogalactosylation in HLA-DRB1 SE-positive patients with higher CRP levels suggests that antigen presentation in the context of SE is associated with a stronger proinflammatory immune activation prior to the involvement and differentiation of B cells, which seem to produce less IgG-galactosylating enzymes than plasma cells and thus would generate more hypogalactosylated IgG. These steps may depend on the extent of monocyte involvement, which contributes to the chronic inflammatory response by increased production, preterm release from bone marrow, reduced circulation time, and activation in the joint as reported recently [ 53 ]. Furthermore, HLA-DRB4, which is preferentially connected to the HLA-DRB1 SE, may exhibit differential effects on immune activation [ 54 ].…”

Children with oligoarticular Juvenile Idiopathic Arthritis have skewed synovial monocyte polarization pattern with functional impairment – a distinct inflammatory pattern for oligoarticular juvenile arthritis

“…In these patients, we observed an increased surface expression of CD163 in synovial uid monocytes compared to monocytes from oligoarticular patients. In addition, CD163 has been linked to several adult arthritides, including increased expression in RA synovial uid monocytes, and following stimulation of monocytes-derived macrophages with synovial uid from SpA patients (15,24). M2(IL-10) like macrophages correlate with in ammatory features in SpA (25,26).…”

Ab0122 tnf Inhibition in Rheumatoid Arthritis Responders to Certolizumab-Pegol Reduces Lymphocyte Recruitment From Blood While Monocyte Turnover Remains Increased

“…PloS one, 9(2), e85784. 1 , the most characteristic observation was the reduced absolute number of non-classical CD16 + CD14 low monocytes at baseline when compared to healthy controls. This corresponds to increased monocyte turnover and recruitment to inflamed tissue.…”