Dysregulated Fc receptor function in active rheumatoid arthritis

Magnusson, Sofia; Wennerberg, Erik; Matt, Peter; Lindqvist, Ulla; Kleinau, Sandra

doi:10.1016/j.imlet.2014.08.016

Cited by 25 publications

(28 citation statements)

References 39 publications

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“…However, the data on this are far from consistent. Some studies found no differences between RA patients and healthy controls ( 60 , 64 – 66 ), whereas others reported that monocytes, mo-DCs, monocyte-derived macrophages, and synovial macrophages of RA patients displayed elevated levels of activating receptors FcγRIIa and FcγRIII, while expression of inhibitory receptor FcγRIIb was similar to healthy controls ( 9 , 10 , 29 , 57 , 67 , 68 ) (Figure 2 A). The reasons for these inconsistent findings are still unclear, but may involve differences in the stage of disease, donor variation, and disease heterogeneity.…”

Section: Autoimmunity: Undesired Fcγr-induced Cytokine Productionmentioning

confidence: 95%

“…In the context of RA, FcγR stimulation on myeloid cells has been shown to induce pro-inflammatory cytokines that are pivotal in RA pathogenesis, including TNFα, IL-1β, and IL-6. Precipitated or plate-bound IgG from serum or synovial fluid of RA patients, without any additional stimulus, induces TNFα production by healthy donor PBMC, predominantly monocytes, in an FcγRIIa-dependent manner ( 55 – 57 ). However, in these experiments, the resulting levels of TNFα were rather low (picogram-range), which indicates the marginal capacity of FcγRs to induce cytokine production when stimulated without any co-stimulation.…”

Section: Autoimmunity: Undesired Fcγr-induced Cytokine Productionmentioning

confidence: 99%

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Control of Cytokine Production by Human Fc Gamma Receptors: Implications for Pathogen Defense and Autoimmunity

et al. 2015

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Control of cytokine production by immune cells is pivotal for counteracting infections via orchestration of local and systemic inflammation. Although their contribution has long been underexposed, it has recently become clear that human Fc gamma receptors (FcγRs), which are receptors for the Fc region of immunoglobulin G (IgG) antibodies, play a critical role in this process by controlling tissue- and pathogen-specific cytokine production. Whereas individual stimulation of FcγRs does not evoke cytokine production, FcγRs cell-type specifically interact with various other receptors for selective amplification or inhibition of particular cytokines, thereby tailoring cytokine responses to the immunological context. The physiological function of FcγR-mediated control of cytokine production is to counteract infections with various classes of pathogens. Upon IgG opsonization, pathogens are simultaneously recognized by FcγRs as well as by various pathogen-sensing receptors, leading to the induction of pathogen class-specific immune responses. However, when erroneously activated, the same mechanism also contributes to the development of autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. In this review, we discuss control of cytokine production as a novel function of FcγRs in human innate immune cells in the context of homeostasis, infection, and autoimmunity and address the possibilities for future therapeutic exploitation.

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Section: Autoimmunity: Undesired Fcγr-induced Cytokine Productionmentioning

confidence: 95%

Section: Autoimmunity: Undesired Fcγr-induced Cytokine Productionmentioning

confidence: 99%

Control of Cytokine Production by Human Fc Gamma Receptors: Implications for Pathogen Defense and Autoimmunity

et al. 2015

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“…We have recently shown that the FcγR expression on monocytes/macrophages is modified in established RA and that patients with an active disease have a dysregulated FcγR function despite ongoing anti-rheumatic treatment [ 42 ]. In order to extend our knowledge of monocyte FcR activity in the early phase of RA, we conducted a study on drug-naïve, auto-ab-positive early RA patients.…”

Section: Introductionmentioning

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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“…The over‐secretion of CD32B by B cells has been shown to reduce the incidence of SLE mouse model . It has been reported that CD32B was increased on dendritic cells in untreated RA subjects with a low disease activity . Studies focused on FcγRs expression of thyrocytes from AITD suggested CD32B and FcRn may participate in the autoantigen presenting .…”

Section: Discussionmentioning

confidence: 99%

“…26 It has been reported that CD32B was increased on dendritic cells in untreated RA subjects with a low disease activity. 27 Studies focused on FcγRs expression of thyrocytes from AITD suggested CD32B and FcRn may participate in the autoantigen presenting. 16,20 Our study here demonstrated that the expression of inhibitory CD32B from PBMC was also downregulated in GD patients, providing further evidence to confirm CD32B could be involved in the pathogenesis of GD.…”

Section: Discussionmentioning

confidence: 99%

Decreased expression of FcγRII in active Graves' disease patients

Peng

Wang

et al. 2019

Clinical Laboratory Analysis

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BackgroundGraves' disease (GD) is a common autoimmune disease characterized by genetic and environmental factors. Fcγ receptors (FcγRs) are involved in several autoimmune disorders through recognizing immunoglobulin (Ig) G antibodies and mediating immune response. The study on the expression of FcγRs in GD patients is scarce. The purpose of this study was to evaluate the expression of three different types of FcγRs in patients with active and remissive GD.MethodsBlood samples of patients and healthy subjects were collected to analyze the percentage of FcγRI (CD64), FcγRII (CD32), and FcγRIII (CD16) on peripheral blood mononuclear cells (PBMCs) and monocytes by flow cytometry and Western blotting. CD32 isotypes were also examined in cases and controls by real‐time PCR.ResultsThe cell percentages expressed CD32 and protein expressions of CD32 on PBMCs, and monocytes from patients with active GD were significantly reduced compared to controls and patients with remissive GD. In particular, the expression of CD32B on PBMC was also decreased in active GD patients. However, the cell percentages expressed CD16 and CD64 from PBMCs and monocytes were comparable between three groups. Besides, the percentages of CD14+CD32+ cells were negatively correlated with TRAb titers in active GD patients (r = −0.5825, P ＜ 0.001).ConclusionThese results suggested that CD32 may act as a novel marker for active GDs. The expression of monocytic CD32, in particular CD32B, in GD patients might play a crucial role in maintaining FcγRs function and be a therapeutic target in GD patients.

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Dysregulated Fc receptor function in active rheumatoid arthritis

Cited by 25 publications

References 39 publications

Control of Cytokine Production by Human Fc Gamma Receptors: Implications for Pathogen Defense and Autoimmunity

Control of Cytokine Production by Human Fc Gamma Receptors: Implications for Pathogen Defense and Autoimmunity

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

Decreased expression of FcγRII in active Graves' disease patients

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