Alterations in peripheral blood memory B cells in patients with active rheumatoid arthritis are dependent on the action of tumour necrosis factor

INTRODUCTION: Disturbances in peripheral blood memory B cell subpopulations have been observed in various autoimmune diseases, but have not been fully delineated in rheumatoid arthritis (RA). Additionally, the possible role of tumour necrosis factor (TNF) in regulating changes in specific peripheral blood memory B cell subsets in RA is still unclear. METHODS: The frequency and distribution of B cell subsets in the peripheral blood and synovial membrane of active RA patients with long-standing disease have been analysed. Additionally, the possible role of TNF in causing disturbances in memory B cell subsets in RA patients was assessed in a clinical trial with the specific TNF-neutralising antibody, infliximab. RESULTS: RA patients, independent of disease duration, have a significantly lower frequency of peripheral blood pre-switch IgD+CD27+ memory B cells than healthy individuals, whereas post-switch IgD-CD27+ accumulate with increased disease duration. Notably, both pre-switch IgD+CD27+ and post-switch IgD-CD27+ memory B cells accumulate in the synovial membrane of RA patients. Finally, anti-TNF therapy increased the frequency of pre-switch IgD+CD27 memory B cells in the peripheral blood. CONCLUSIONS: The data suggest that decreases in peripheral blood IgD+CD27+ pre-switch memory B cells in RA reflect their accumulation in the synovial tissue. Moreover, the significant increase in the peripheral blood pre-switch memory B cells in patients who underwent specific TNF-blockade with infliximab indicates that trafficking of memory B cells into inflamed tissue in RA patients is regulated by TNF and can be corrected by neutralising TN

Size effects on antimicrobial efficiency of DBD plasma coated silver nanoparticles on textiles

This work studies the surface characteristics, the antimicrobial activity and the aging effect, of plasma pre-treated polyamide 6,6 fabrics (PA66) coated with silver nanoparticles (AgNPs), with the aim to identify the optimum size of nanosilver exhibiting antibacterial properties suitable for manufacturing of hospital textiles. The release of bactericidal Ag+ ions from the 10, 20, 40, 60 and 100 nm AgNPs-coated PA66 surface were function of the particles size, number and aging. Plasma pre-treatment promoted both ionic and covalent interactions between AgNPs and the formed oxygen species on the fibers (Figure 1), favoring the deposition of smaller in diameter AgNPs that consequently showed better immediate and durable antimicrobial effect against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus bacteria. Surprisingly, after 30 days of aging, a comparable bacterial growth inhibition was achieved for all the fibers treated with AgNPs of <100 nm in size. The Ag+ in the coatings also favored the electrostatic stabilization of the plasma-induced functional groups on the PA66 surface, thereby retarding the aging process (Figure 2). At the same time, the size-related ratio Ag+/Ag0 of the AgNPs between 40 and 60 nm allowed for controlled release of Ag+ rather than bulk silver. Overall, the results suggest that instead of reducing the AgNPs size, which is associated to higher toxicity, similar long-term effects can be achieved with larger NPs (40-60 nm), even in lower concentrations. Since the antimicrobial efficiency of AgNPs larger than 30 nm is mainly ruled by the release of Ag+ over time and not by the size and number of the AgNPs, this parameter is crucial for the development of efficient antimicrobial coatings on plasma-treated surfaces, and contribution to the safety and durability of clothing used in clinical settings

Size and aging effects on antimicrobial efficiency of silver nanoparticles coated on polyamide fabrics activated by atmospheric DBD plasma

Recently, renewed interest has arisen in silver nanopar@cles for biomedical devices because of their high surface energy, enhanced physicochemical and biological proper@es and extremely large surface area, which provides beAer contact with microorganisms. Atmospheric plasma is an alterna@ve and cost- compe@@ve method to wet chemical nanopar@cles deposi@on methods, avoiding the need of toxic solvents, expensive vacuum equipment and allowing con@nuous and uniform processing of material surfaces. However, there are no reports on the size and @me-dependent an@microbial, physical and chemical surface effects of the silver nanopar@cles immobilized on plasma func@onalized polymers. Thus, the purposes of this study were: (i) the silver nanopar@cle size and aging effects aCer 30 days on the an@microbial ac@vity aCer deposi@on onto DBD plasma-treated polyamide 6,6 fabrics, and (ii) the aging effect on the physico-chemical binding mechanism between different sized silver nanopar@cles and the plasma treaded polyamide 6,6. Five different in size commercial silver nanopar@cles have been employed (10, 20, 40 60 and 100 nm).This work was funded by Portuguese Founda@on for Science and Technology FCT/MCTES (PIDDAC) and co-financed by European funds (FEDER) through the PT2020 program, research project M-ERA-NET/0006/2014 and COMPETE program through FCT within the scope of the project POCI-01-0145-FEDER-007136 and UID/CTM/00264.info:eu-repo/semantics/publishedVersio

Reactive Oxygen Species Deficiency Due to Ncf1-Mutation Leads to Development of Adenocarcinoma and Metabolomic and Lipidomic Remodeling in a New Mouse Model of Dextran Sulfate Sodium-Induced Colitis

Inflammatory bowel disease is characterized by chronic relapsing idiopathic inflammation of the gastrointestinal tract and persistent inflammation. Studies focusing on the immune-regulatory function of reactive oxygen species (ROS) are still largely missing. In this study, we analyzed an ROS-deficient mouse model leading to colon adenocarcinoma. Colitis was induced with dextran sulfate sodium (DSS) supplied via the drinking water in wild-type (WT) and Ncf1-mutant (Ncf1) B10.Q mice using two different protocols, one mimicking recovery after acute colitis and another simulating chronic colitis. Disease progression was monitored by evaluation of clinical parameters, histopathological analysis, and the blood serum metabolome using 1H nuclear magnetic resonance spectroscopy. At each experimental time point, colons and spleens from some mice were removed for histopathological analysis and internal clinical parameters. Clinical scores for weight variation, stool consistency, colorectal bleeding, colon length, and spleen weight were significantly worse for Ncf1 than for WT mice. Ncf1 mice with only a 7-day exposure to DSS followed by a 14-day resting period developed colonic distal high-grade dysplasia in contrast to the low-grade dysplasia found in the colon of WT mice. After a 21-day resting period, there was still β-catenin-rich inflammatory infiltration in the Ncf1 mice together with high-grade dysplasia and invasive well-differentiated adenocarcinoma, while in the WT mice, high-grade dysplasia was prominent without malignant invasion and only low inflammation. Although exposure to DSS generated less severe histopathological changes in the WT group, the blood serum metabolome revealed an increased fatty acid content with moderate-to-strong correlations to inflammation score, weight variation, colon length, and spleen weight. Ncf1 mice also displayed a similar pattern but with lower coefficients and showed consistently lower glucose and/or higher lactate levels which correlated with inflammation score, weight variation, and spleen weight. In our novel, DSS-induced colitis animal model, the lack of an oxidative burst ROS was sufficient to develop adenocarcinoma, and display altered blood plasma metabolic and lipid profiles. Thus, oxidative burst seems to be necessary to prevent evolution toward cancer and may confer a protective role in a ROS-mediated self-control mechanism

CD8+T cell profiles in patients with rheumatoid arthritis and their relationship to disease activity

Objective CD8+T cells are abundant in rheumatoid arthritis (RA). However, their role in the disease pathogenesis is poorly defined. Here we investigated the relationship between disease activity and CD8+T cell phenotypes, production of cytokines and cytotoxic molecules in RA peripheral blood (PB) and synovial fluid (SF). Methods CD8+T cell phenotypes were determined in 96 patients with RA (44 in remission, 34 with active disease) and in 64 gender and age-matched healthy controls (HC). Ten paired PB and SF samples from patients with active RA were analyzed. The expression of surface markers, cytokines and proteolytic enzymes in CD8+T cells was evaluated using flow-cytometry. Results The PB CD8+T cells from RA patients with active disease exhibited an effector CD27-CD62L- (p=0.005) phenotype with elevated proinflammatory cytokine expression (TNF-α, IFN-γ, IL-6, IL-17A) when compared to HC. The phenotype observed in patients with active disease persisted in remission, with a significant increase in the frequency of CD69 (p<0.001) and was associated with lower cytokine production. CD8+T cells from SF expressed more robust effector memory (CD27+CD62L-) and activated (CD69+) profiles compared with paired blood-derived subsets. Cytokine-production (IL-6, IL-17A, and IFN-γ) by CD8+T cells from PB and SF was positively correlated within individual donors. The production of cytokines (TNF-α, IFN-γ, IL-17A) by CD8+T cells in the PB from RA patients positively correlated with DAS28. Conclusion Herein we characterize the activation status and proinflammatory potential of CD8+T cells subsets in RA patients. This activation status strongly suggests a local and systemic effector cytotoxic role in the disease

CD8+ T cell profiles in patients with rheumatoid arthritis and their relationship to disease activity

Objective. CD8+ T cells are abundant in rheumatoid arthritis (RA). However, their role in disease pathogenesis is poorly defined. This study was undertaken to investigate the relationship between disease activity and CD8+ T cell phenotypes, production of cytokines, and production of cytotoxic molecules in the peripheral blood (PB) and synovial fluid (SF) of patients with RA. Methods. CD8+ T cellw phenotypes were determined in 96 patients with RA (44 with disease in remission, 34 with active disease, 18 with low disease activity) and in 64 sex- and age-matched healthy controls. Ten paired PB and SF samples from patients with active RA were analyzed. The expression of surface markers, cytokines, and proteolytic enzymes in CD8+ T cells was evaluated using flow cytometry. Results. PB CD8+ T cells from RA patients with active disease exhibited an effector (CD27-CD62L-) phenotype (P = 0.005), with elevated expression of proinflammatory cytokines (tumor necrosis factor α [TNFα], interferon-γ [IFNγ], interleukin-6 [IL-6], IL-17A) when compared to healthy controls. In a state of remission, the same phenotype observed in patients with active disease persisted, including a significant increase in the frequency of CD69 (P <0.001), but lower cytokine production was observed. SF CD8+ T cells from RA patients expressed more robust effector memory (CD27+CD62L-) and activated (CD69+) profiles compared to the T cell subsets in paired PB samples. Production of cytokines (IL-6, IL-17A, and IFNγ) by CD8+ T cells from RA PB was positively correlated within individual donors. Moreover, production of cytokines (TNFα, IFNγ, and IL-17A) by CD8+ T cells from RA PB positively correlated with the Disease Activity Score in 28 joints. Conclusion. The activation status and proinflammatory potential of CD8+ T cell subsets observed in the RA patients in this study strongly suggest that a phenotype of local and systemic cytotoxic effector T cells plays a role in this disease