311 research outputs found
Obesity as a Risk and Severity Factor in Rheumatic Diseases (Autoimmune Chronic Inflammatory Diseases)
The growing body of evidence recognizing the adipose tissue as an active endocrine organ secreting bioactive mediators involved in metabolic and inflammatory disorders, together with the global epidemic of overweight and obesity, rise obesity as a hot topic of current research. The chronic state of low grade inflammation present in the obese condition and the multiple pleiotropic effects of adipokines on the immune system has been implicated in the pathogenesis of several inflammatory conditions including rheumatic autoimmune and inflammatory diseases. We will discuss the main relevant evidences on the role of the adipose tissue on immune and inflammatory networks and the more recent evidences regarding the effects of obesity on the incidence and outcomes of the major autoimmune chronic inflammatory diseases
MicroRNA-155āat the critical interface of innate and adaptive immunity in arthritis
MicroRNAs (miRNAs) are small non-coding RNAs that fine-tune the cell response to a changing environment by modulating the cell transcriptome. MiR-155 is a multifunctional miRNA enriched in cells of the immune system and is indispensable for the immune response. However, when deregulated, miR-155 contributes to the development of chronic inflammation, autoimmunity, cancer and fibrosis. Herein, we review the evidence for the pathogenic role of miR-155 in driving aberrant activation of the immune system in Rheumatoid Arthritis, and its potential as a disease biomarker and therapeutic target
ZAP-70+ B Cell Subset Influences Response to B Cell Depletion Therapy and Early Repopulation in Rheumatoid Arthritis
Objective.To define the role of ZAP-70+ B cells (CD19+/ZAP-70+) as a biomarker of response to B cell depletion therapy (BCDT), their relationship with clinical outcome, and their behavior during repopulation of peripheral blood in patients with rheumatoid arthritis (RA).Methods.Thirty-one patients with RA underwent BCDT and were followed for 12 months. Disease activity was assessed with the European League Against Rheumatism (EULAR) criteria. Cytofluorimetric analysis of peripheral blood B cell subsets at baseline and at 6- and 12-month intervals after BCDT was performed using surface markers (CD45, CD3, CD56, CD19, IgD, CD38, CD27) and intracellular ZAP-70.Results.A moderate/good EULAR response was achieved in 66.6% of the RA cohort. The baseline percentage of CD19+/ZAP-70+ cells was lower in good responder patients (1.8% Ā± 1.7%) compared to poor responders (5.6% Ā± 4.9%; p = 0.02). A decrease of plasmablasts (IgD-CD27+CD38+) and pre-switch memory (IgD+CD27+) B cells occurred after BCDT. Recovery of B cells in peripheral blood after the first course of BCDT was characterized by the reappearance of B cell subtypes that showed a naive, activated phenotype, coupled with a decrease in memory cells. B cells carrying intracytoplasmic ZAP-70 increased significantly from the baseline value of 4.4% Ā± 4.5% to 12.4% Ā± 9.2% (p = 0.001) at the 6-month and to 9.4% Ā± 6.4% (p = 0.002) at the 12-month followup.Conclusion.Baseline percentage of CD19+/ZAP-70+ cells is associated with the clinical outcome after BCDT in patients with RA. Depletion of plasmablasts and pre-switch memory B cells and increase of CD19+/ZAP-70+ cells are features of the recovery of the B cell pool after BCDT
Very early rheumatoid arthritis is the major predictor of major outcomes: clinical ACR remission and radiographic non-progression
OBJECTIVES: To identify predictors of clinical remission as well as of no x-ray
progression in a cohort of early rheumatoid arthritis (ERA) treated with a
tight-control protocol.
METHODS: A total of 121 consecutive patients with ERA were treated to reach
European League Against Rheumatism (EULAR) and/or American College of
Rheumatology (ACR) clinical remission with methotrexate (MTX) for 3 months, then
with a combination with anti-tumour necrosis factor if the patient did not
achieve a 44-joint Disease Activity Score (DAS44) ā¤2.4. At baseline and after 12
months all the patients had hand and foot joint radiographs. Very early
rheumatoid arthritis (VERA) was defined as a disease with symptoms of less than
12 weeks.
RESULTS: In all, 46.3% of the patients reached DAS remission and 24.8% achieved
ACR remission. More than 60% of patients reached remission with MTX. Male sex and
an erythrocyte sedimentation rate <35 mm/h at onset arose as significant
predictors of EULAR remission, while VERA disease was the only predictor of ACR
remission. At baseline, 28.1% of the patients were erosive. Multivariate analysis
demonstrated that the only independent predictor of erosiveness was 'not having
VERA disease'. After 12 months, VERA was the only factor predicting a lack of new
erosions.
CONCLUSIONS: VERA represents the best therapeutic opportunity in clinical
practice to achieve a complete remission and to stop the erosive course of
rheumatoid arthritis
Memory B cell subsets and plasmablasts are lower in early than in long-standing Rheumatoid Arthritis
Alterations of B cell subset distribution have been described in the peripheral blood (PB) of rheumatoid arthritis (RA) patients, but no data are available on differences between the onset and the established phases of the disease. The purpose of the study was to clarify whether a peculiar distribution of B cell subsets characterizes RA onset, thus leading to a more favorable clinical response to treatment, and to evaluate the possible association of a particular B cell subpopulation with response to therapy
MicroRNA-155 influences B-cell function through PU.1 in rheumatoid arthritis
MicroRNA-155 (miR-155) is an important regulator of B cells in mice. B cells have a critical role in the pathogenesis of rheumatoid arthritis (RA). Here we show that miR-155 is highly expressed in peripheral blood B cells from RA patients compared with healthy individuals, particularly in the IgD-CD27- memory B-cell population in ACPA+ RA. MiR-155 is highly expressed in RA B cells from patients with synovial tissue containing ectopic germinal centres compared with diffuse synovial tissue. MiR-155 expression is associated reciprocally with lower expression of PU.1 at B-cell level in the synovial compartment. Stimulation of healthy donor B cells with CD40L, anti-IgM, IL-21, CpG, IFN-Ī±, IL-6 or BAFF induces miR-155 and decreases PU.1 expression. Finally, inhibition of endogenous miR-155 in B cells of RA patients restores PU.1 and reduces production of antibodies. Our data suggest that miR-155 is an important regulator of B-cell activation in RA
The Role of High-Mobility Group Box-1 and Its Crosstalk with Microbiome in Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a chronic, definitely disabling, and potentially severe autoimmune disease. Although an increasing number of patients are affected, a key treatment for all patients has not been discovered. High-mobility group box-1 (HMGB1) is a nuclear protein passively and actively released by almost all cell types after several stimuli. HMGB1 is involved in RA pathogenesis, but a convincing explanation about its role and possible modulation in RA is still lacking. Microbiome and its homeostasis are altered in patients with RA, and the microbiota restoration has been proposed to patients with RA. The purpose of the present review is to analyze the available evidences regarding HMGB1 and microbiome roles in RA and the possible implications of the crosstalk between the nuclear protein and microbiome in understanding and possibly treating patients affected by this harmful condition
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