Up-regulation of CD64-expressing monocytes with impaired FcγR function reflects disease activity in polyarticular psoriatic arthritis

Matt, Peter; Lindqvist, Ulla; Kleinau, Sandra

doi:10.3109/03009742.2015.1020864

Cited by 12 publications

(8 citation statements)

References 45 publications

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“…The pathways identified as enriched among the PsA‐associated genes were neutrophil granulation, NOTCH4 and NOTCH3 signaling, and IL‐4 and IL‐13 signaling. The finding that myeloid gene sets are upregulated in disease is consistent with prior reports of increased myeloid cell types, including CD64+ and CD14+CD16+ monocytes, in the blood of patients with PsA, although further study is needed to better define the immune cells identified to be affected in this analysis (27,28).…”

Section: Discussionsupporting

confidence: 88%

Guselkumab Modulates Differentially Expressed Genes in Blood of Patients With Psoriatic Arthritis: Results from Two Phase 3, Randomized, Placebo‐Controlled Trials

Siebert

Sweet

Ritchlin

et al. 2023

ACR Open Rheumatology

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ObjectiveTo evaluate gene expression in blood of patients with psoriatic arthritis (PsA) versus healthy controls and identify changes associated with guselkumab treatment.MethodsWhole blood transcriptome profiling via paired‐end RNA sequencing was conducted using samples from DISCOVER‐1 and DISCOVER‐2 at baseline (n = 673) and at weeks 4 and 24 from a representative subgroup that received placebo or guselkumab (n = 227 [longitudinal PsA cohort]). Baseline samples were compared with demographically matched healthy controls (n = 21). Guselkumab‐mediated changes in gene expression were assessed in participants from the longitudinal PsA cohort who did versus did not achieve at least 20% improvement in American College of Rheumatology response criteria (ACR20) or at least 75% improvement in Psoriasis Area and Severity Index (PASI75). Differential gene expression was analyzed using edgeR.ResultsAt baseline, 355 upregulated and 314 downregulated genes (PsA‐associated genes) were identified in patients with PsA versus healthy controls. Upregulated genes were related to neutrophil, mononuclear cell, and CD11b+ gene sets. No cell type–specific gene sets were identified among downregulated genes. Most PsA‐associated genes were modulated by guselkumab treatment. At week 24, genes downregulated by guselkumab were enriched with neutrophil, monocyte, eosinophil, and macrophage gene sets; genes upregulated by guselkumab were enriched with B cell, T cell, and natural killer cell gene sets. Reductions in expression of upregulated PsA‐associated gene sets were more pronounced in ACR20 and PASI75 responders than in nonresponders.ConclusionThese findings suggest a dysregulation of immune cell profiles in blood from patients in the baseline PsA cohort that approached levels in healthy controls after guselkumab treatment.

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Section: Discussionsupporting

confidence: 88%

Guselkumab Modulates Differentially Expressed Genes in Blood of Patients With Psoriatic Arthritis: Results from Two Phase 3, Randomized, Placebo‐Controlled Trials

Siebert

Sweet

Ritchlin

et al. 2023

ACR Open Rheumatology

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“…The increase in CD64 on monocytes was previously associated with their increased phagocytosis capacity and inversely correlated with their TNFa secretion in various inflammatory pathologies. 23,24 However, it was out of the scope of this study to evaluate the cell functions.…”

Section: Discussionmentioning

confidence: 99%

Distinct effect of age, sex, and CMV seropositivity on dendritic cells and monocytes in human blood

et al. 2017

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We analyzed the impact of age, sex, and CMV on blood monocyte and dendritic cell (DC) subpopulations in 256 healthy individuals aged from 19 to 96 years. Flow cytometry was performed on whole blood within the 4 h following blood drawing. Myeloid (mDC) and plasmacytoid DC (pDC), classical, intermediate, and nonclassical monocytes were enumerated by means of TruCount tubes (BD Biosciences). We provided reference values for mDC, pDC and the three monocyte subpopulations. The numbers of classical, intermediate, and nonclassical monocytes slightly increased with age while the numbers of mDC and pDC did not vary significantly. The level of expression of CD64 and CD163 on monocytes significantly increased with age while HLA-DR expression did not vary significantly. More precisely, CD163 expression level on intermediate monocyte slightly increased with age in women only (Spearman P = 0.019) while CD64 expression increased on monocytes in CMV-positive individuals only. We observed that sex had almost no impact on the numbers of monocytes and DC and on their expression level of CD64 and HLA-DR. We observed a significant decrease in the numbers of pDC with age in CMV-positive individuals, but not in CMV negative individuals. This suggests that the lifelong subclinical infection by CMV could influence the number of circulating DC of lymphoid origin. In contrast, CMV serostatus had no significant impact on absolute numbers of mDC and monocytes.

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“…SEB278Hu; Cloud-Clone Corp, USA) according to the Manufacturers' recommendations. For comparison, plasma samples from 20 age- and sex-matched psoriatic arthritis patients with active polyarticular disease (mean DAS28 = 4.1) were analyzed (the characteristics of these are presented in [ 47 ]). Briefly, microtiter plates pre-coated with anti-human CD89, CD64 or CD16a capture abs were incubated at 37°C for 2 h with 100 μl/well of standard (in a 2-fold dilution series) or thawed plasma samples in duplicate.…”

Section: Methodsmentioning

confidence: 99%

Elevated Membrane and Soluble CD64: A Novel Marker Reflecting Altered FcγR Function and Disease in Early Rheumatoid Arthritis That Can Be Regulated by Anti-Rheumatic Treatment

2015

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ObjectivesFc receptors (FcR) interacting with immune complexes (ICs) is a central event in the immune pathogenesis of rheumatoid arthritis (RA). Here we asked if a specific FcR is linked to RA pathogenesis and if FcR activities relate to disease and treatment outcome in early RA.Material and MethodsTwenty autoantibody-positive RA patients and 33 HC were included. The patients were evaluated before and after treatment with methotrexate and prednisolone. At follow-up, the EULAR response criteria were applied to determine the individual treatment outcomes. Serum immunoglobulin levels were measured and the expression of FcR for IgG (FcγR) and IgA (FcαR) on peripheral blood monocytes were determined by flow cytometry. The monocytic FcγR function was evaluated by human IgG1 and IgG3 IC-binding and TNFα stimulated release. Plasma levels of soluble FcRs (sFcRs) were determined with ELISA.ResultsThe IgG1 and IgG3 levels were elevated in the RA sera. The RA monocytes expressed more CD64 and cell surface-bound IgG than HC monocytes, and showed an impaired FcγR function as reflected by changes in IC-binding and decreased IC-stimulated TNFα secretion. These findings correlated significantly with different disease activity markers. Furthermore, sFcRs were elevated in the patient plasma, and sCD64 was specific for RA (compared with a reference group of patients with active psoriatic arthritis). Following treatment, immunoglobulins and sFcR levels were reduced, whereas membrane CD64 was only decreased in patients with good response to treatment.ConclusionsEarly RA patients display increased membrane and soluble CD64 and an impaired FcγR function correlating with joint disease activity. Beneficial responses of anti-rheumatic treatment in patients reduce CD64. These data suggest sCD64 as an important objective biomarker in RA.

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Up-regulation of CD64-expressing monocytes with impaired FcγR function reflects disease activity in polyarticular psoriatic arthritis

Cited by 12 publications

References 45 publications

Guselkumab Modulates Differentially Expressed Genes in Blood of Patients With Psoriatic Arthritis: Results from Two Phase 3, Randomized, Placebo‐Controlled Trials

Guselkumab Modulates Differentially Expressed Genes in Blood of Patients With Psoriatic Arthritis: Results from Two Phase 3, Randomized, Placebo‐Controlled Trials

Distinct effect of age, sex, and CMV seropositivity on dendritic cells and monocytes in human blood

Elevated Membrane and Soluble CD64: A Novel Marker Reflecting Altered FcγR Function and Disease in Early Rheumatoid Arthritis That Can Be Regulated by Anti-Rheumatic Treatment

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