1,721,087 research outputs found
Infectious agents breaking the immunological tolerance: The holy grail in rheumatoid arthritis reconsidered
Full text linkMultiple Sclerosis (MS) has been shown to be linked to Epstein Barr Virus (EBV) infection, a virus that infects B cells inside the CNS. The seminal study raises a key interest into the infectious origin of several other autoimmune inflammatory diseases.We will discuss here the infectious agents that have been studied over the years in Rheumatoid Arthritis (RA), a crippling arthritis that was treated a century ago with gold salts (anti mycobacterial agent), chloroquine (anti malarial agent), or sulphasalazine (an antibacterial-antiinflammatory agent). Several infectious agents have been taken into consideration, i.e. Streptococcus group A, Proteus, Mycobacterium tuberculosis-MTB, Parvovirus B19, Epstein Barr virus, Porphyromonas gingivalis-Pg, Aggregatibacter actinomycetescomitans, and finally Haemophilus-Glaesserella parasuis-Hps. Of these agents only three satisfy the Witebski's criteria as possible pathogenetic causes of an autoimmune disease, i.e. MTB, Pg, Hps. We will discuss here how the immune tolerance might be broken, which could be the neoantigen or autoantigen involved, how the infectious agent was studied as a trigger capable of inducing arthritis in animal models. The preventive measures that should be adopted to lessen the impact of the infections, to prevent the burden and the severity of the illness are described
Do we need to apply a T2T strategy even in ACPA-negative early rheumatoid arthritis? YES
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Could we use a lower dose of rituximab to treat rheumatoid arthritis in clinical practice: Pros and cons?
Full text linkThe CERERRA database provides evidence that low-dose rituximab performs as well as the conventional dose in the real world, thus highlighting the possible pharmacoeconomic impact. In clinical trials, it has been shown that rituximab 500 mg twice, performs as well as 1 g twice, 2 weeks apart, in terms of the American College of Rheumatology (ACR)20 and ACR50, but not the ACR70. The choice should always be made after considering that the IMAGE trial has demonstrated similar radiographic progression after the first 6 months, but with less control, with low-dose rituximab in the first 6 months. A possible alternative can be hypothesized
Weight Loss, The Obesity Paradox in Rheumatoid Arthritis: Is It a Paradox? Comment on the Article by Baker et al
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Concentrations of BAFF correlate with autoantibody levels, clinical disease activity, and response to treatment in early rheumatoid arthritis
No full textObjective: To determine whether levels of B cell activating factor (BAFF), a member of the tumor necrosis factor family, relate to autoantibody levels, disease activity, and response to treatment in patients with early rheumatoid arthritis (ERA). Methods: BAFF was measured by ELISA in 48 early RA patients; 21 were examined serially. These data were compared with 49 controls with longstanding RA (LSRA), 48 disease controls (DC), and 50 healthy controls (HC). Results: BAFF levels were higher in ERA, compared with DC and HC [median 4.3 ng/ml (5th-95th: 0.8-38.8) vs 0.9 ng/ml (5th-95th: 0.7-4.5) and 2.0 ng/ml (5th-95th: 0.7-5.68), respectively; p <10(-4 )both comparisons], but not with LSRA controls [median 8.7 ng/ml (5th-95th: 0.8-46.1); p = nonsignificant]. BAFF correlated with the titers of IgM rheumatoid factor and anti-cyclic citrullinated peptide autoantibody (r = 0.76 and r = 0.49; p < 0.00001, p = 0.0001 for the 2 correlations), and with the number of swollen joints (r = 0.37; p = 0.01). The followup study of 21 methotrexate-treated ERA patients revealed reduced levels of BAFF, with parallel improvement in clinical activity and decrease in autoantibody titers. Conclusion: Elevated BAFF in a subset of ERA patients is related to autoantibody levels and synovitis. BAFF level diminished with treatment, along with autoantibody titers, suggesting a rationale to treat ERA patients with BAFF-targeted agents
ZAP-70+ B Cell Subset Influences Response to B Cell Depletion Therapy and Early Repopulation in Rheumatoid Arthritis
No full textOBJECTIVE: 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% ± 1.7%) compared to poor responders (5.6% ± 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% ± 4.5% to 12.4% ± 9.2% (p = 0.001) at the 6-month and to 9.4% ± 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
Should rheumatoid factor (RF) (and antinuclear antibodies (ANA)) become routinary screening test for morbidities in the general population?: From the concept of “benign autoimmunity “to the concept of” autoimmunity as a red flag in preventive medicine”?
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MicroRNA-155-at the Critical Interface of Innate and Adaptive Immunity in Arthritis.
Full text linkMicroRNAs (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
Amplifying the concept of psoriatic arthritis: The role of autoimmunity in systemic psoriatic disease
No full textPsoriatic arthritis (PsA) is a chronic inflammatory arthritis that may be present in near 30% of patients affected by psoriasis (PsO), clinically characterized by inflammation of periarticular (e.g., enthesis) and articular structures. Recently, an autoimmune footprint of PsA pathogenesis has been demonstrated with the presence of autoantigens and related autoantibodies in PsA patients' sera. In this context, histological features of PsA synovitis supports the relevance of an autoimmune pathogenesis of the disease. Since there is no currently validated test for PsA, the analysis of PsA synovial tissue revealed pathognomonic characteristics of PsA that may support the clinician in the clinical practice. PsA synovitis is characterized by a sublining infiltrate with T and B cells, vascular proliferation and a relative thin lining layer of proliferating intimal synoviocytes. PsA synovial histopathology shows that ectopic lymphoid-neogenesis with an increase of IL-23 expression. These new pathogenetics features and the systemic nature of the disease raised the concept of a Systemic Psoriatic Disease (SysPsD), characterized by multiple extra-cutaneous and –articular manifestations, highlightening the great heterogeneity of this condition. SyPsD represents a heterogeneous chronic inflammatory condition with a wide spectrum of phenotypical manifestations. The purpose of this review is to describe the new pathogenetic mechanisms and the different clinical pictures of SysPsD, with the ultimate goal of improving the knowledge of this heterogeneous chronic inflammatory condition
The B side of rheumatoid arthritis pathogenesis
No full textIn the last years, a dramatic amount of research has been performedincreasing the knowledge about the biological mechanism underpinning Rheumatoid Arthritis (RA) inflammation, putting B lymphocytes in the center of RA pathogenesis. Nowadays, B cell phenotypes and autoantibodies positivity arose as important biomarkers in early and long-standing disease. Moreover, comparative analysis of peripheral blood and synovial tissue compartments enables the identification of novel physiopathological mechanisms promoting inflammation. In this narrative review we will discuss the biological relevance of B cell derived autoimmunity and in RA course, from disease onset to remission achievement
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