Serum CXCL10 levels are associated with better responses to abatacept treatment of rheumatoid arthritis.

Objectives: This study aimed to identify therapeutic predictors of abatacept (ABT) treatment in rheumatoid arthritis (RA) in vitro and in patients.

Methods: T cell cytokine, monokine, and chemokine levels in culture supernatants or serum were determined using flow cytometry bead-based immunoassays. CXCL10 mRNA and protein expressions were also assessed using qPCR and ELISA analyses, respectively.

Risk Factors for Pneumocystis jirovecii Pneumonia in Patients With Rheumatoid Arthritis and a Prophylactic Indication of Trimethoprim/Sulfamethoxazole.

Background/objectives: Immunosuppressant medications (ISPs) increase the occurrence of Pneumocystis jirovecii pneumonia (PCP) in rheumatoid arthritis (RA) patients. The prophylactic administration of trimethoprim/sulfamethoxazole (TMP/SMX) for PCP is effective but has serious adverse effects and so should be selectively used for patients at high risk. The aims of this study were to clarify the risk factors for PCP in RA patients and to establish the indications for administering TMP/SMX.

Pretreatment Prediction of Individual Rheumatoid Arthritis Patients' Response to Anti-Cytokine Therapy Using Serum Cytokine/Chemokine/Soluble Receptor Biomarkers.

Unlabelled: The inability to match rheumatoid arthritis (RA) patients with the anti-cytokine agent most efficacious for them is a major hindrance to patients’ speedy recovery and to the clinical use of anti-cytokine therapy. Identifying predictive biomarkers that can assist in matching RA patients with more suitable anti-cytokine treatment was our aim in this report. The sample consisted of 138 RA patients (naïve and non-naïve) who were administered tocilizumab or etanercept for a minimum of 16 weeks as a prescribed RA treatment.

Comparative evaluation of the effects of treatment with tocilizumab and TNF-α inhibitors on serum hepcidin, anemia response and disease activity in rheumatoid arthritis patients.

Introduction: Anemia of inflammation (AI) is a common complication of rheumatoid arthritis (RA) and has a negative impact on RA symptoms and quality of life. Upregulation of hepcidin by inflammatory cytokines has been implicated in AI. In this study, we evaluated and compared the effects of IL-6 and TNF-α blocking therapies on anemia, disease activity, and iron-related parameters including serum hepcidin in RA patients.

Retreatment efficacy and safety of tocilizumab in patients with rheumatoid arthritis in recurrence (RESTORE) study.

Objectives: To evaluate the safety and efficacy of retreatment with tocilizumab (TCZ) in patients who had participated in the DREAM study (Drug free remission/low disease activity after cessation of tocilizumab [Actemar] monotherapy study) and had experienced loss of efficacy.

Methods: Patients were retreated with TCZ or other disease modifying antirheumatic drugs (DMARDs). Disease activity was measured using the 28-joint disease activity score (DAS28) for 12 weeks.

Drug free REmission/low disease activity after cessation of tocilizumab (Actemra) Monotherapy (DREAM) study.

Objectives: To investigate the duration of remission and low disease activity (LDA) after cessation of tocilizumab (TCZ) treatment in rheumatoid arthritis patients who showed remission or LDA as assessed by DAS28 in response to preceding TCZ monotherapy, and to explore the factors contributing to prolonged efficacy duration.

Methods: Disease activity was monitored for 56 weeks. The rate of continued efficacy was estimated by Kaplan-Meier curves.

Inhibition of TNF-induced IL-6 by the TWEAK-Fn14 interaction in rheumatoid arthritis fibroblast like synoviocytes.

Objectives: TNF-like weak inducer of apoptosis (TWEAK), a member of the TNF superfamily, has been shown to increase cytokine production by rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS). In this study, we determined the effect of interaction between TWEAK and its receptor fibroblast growth factor-inducible-14 (Fn14) on cytokine expression in RAFLS.

Methods: RAFLS were obtained from surgical synovial specimens and used at passage 5-10.

Enhanced induction of LPS-induced fibroblast MCP-1 by interferon-gamma: involvement of JNK and MAPK phosphatase-1.

IFN-gamma has significant immunoregulatory activity and plays an important role in both innate and adaptive immunity. Additive effects of IFN-gamma and the Toll-like receptor ligand LPS has been investigated in macrophages, but in fibroblasts is incompletely understood. IFN-gamma and LPS synergistically induced MCP-1 and NO release in primary murine dermal fibroblasts.

Recruitment of CD16+ monocytes into synovial tissues is mediated by fractalkine and CX3CR1 in rheumatoid arthritis patients.

CD16+ monocytes, identified as a minor population of monocytes in human peripheral blood, have been implicated in several inflammatory diseases, including rheumatoid arthritis (RA). Fractalkine (FKN, CX3CL1), a member of the CX3 C subfamily, is induced by pro-inflammatory cytokines, while a receptor for FKN, CX3CR1, is capable of mediating both leukocyte migration and firm adhesion. Here, we investigated the role of FKN and CX3CR1 in activation of CD16+ monocytes and their recruitment into synovial tissues in RA patients.

Macrophage migration inhibitory factor deficiency attenuates macrophage recruitment, glomerulonephritis, and lethality in MRL/lpr mice.

Systemic lupus erythematosus (SLE) is a serious systemic autoimmune disease of unknown etiology. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that is operative in innate and adaptive immunity and important in immune-mediated diseases such as rheumatoid arthritis and atherosclerosis. The functional relevance of MIF in systemic autoimmune diseases such as SLE is unknown.

Induction of tumour necrosis factor receptor-expressing macrophages by interleukin-10 and macrophage colony-stimulating factor in rheumatoid arthritis.

Despite its potent ability to inhibit proinflammatory cytokine synthesis, interleukin (IL)-10 has a marginal clinical effect in rheumatoid arthritis (RA) patients. Recent evidence suggests that IL-10 induces monocyte/macrophage maturation in cooperation with macrophage-colony stimulating factor (M-CSF). In the present study, we found that the inducible subunit of the IL-10 receptor (IL-10R), type 1 IL-10R (IL-10R1), was expressed at higher levels on monocytes in RA than in healthy controls, in association with disease activity, while their expression of both type 1 and 2 tumour necrosis factor receptors (TNFR1/2) was not increased.

Selective recruitment of CXCR3+ and CCR5+ CCR4+ T cells into synovial tissue in patients with rheumatoid arthritis.

The inflamed synovial tissue (ST) of rheumatoid arthritis (RA) is characterized by the selective accumulation of interferon gamma-producing Th1-type CD4+ T cells. In this study, we investigated whether the predominance of Th1-type CD4+ cells in the ST lesion is mediated by their selective recruitment through Th1 cell-associated chemokine receptors CXCR3 and CCR5. The lymphocyte aggregates in the ST of RA contained a large number of CD4+ T cells, which mostly expressed both CXCR3 and CCR5, but not CCR4.

The S100A8/A9 heterodimer amplifies proinflammatory cytokine production by macrophages via activation of nuclear factor kappa B and p38 mitogen-activated protein kinase in rheumatoid arthritis.

S100A8 and S100A9, two Ca2+-binding proteins of the S100 family, are secreted as a heterodimeric complex (S100A8/A9) from neutrophils and monocytes/macrophages. Serum and synovial fluid levels of S100A8, S100A9, and S100A8/A9 were all higher in patients with rheumatoid arthritis (RA) than in patients with osteoarthritis (OA), with the S100A8/A9 heterodimer being prevalent. By two-color immunofluorescence labeling, S100A8/A9 antigens were found to be expressed mainly by infiltrating CD68+ macrophages in RA synovial tissue (ST).

Increased expression of receptor for advanced glycation end products by synovial tissue macrophages in rheumatoid arthritis.

Objective: The accumulation of advanced glycation end products (AGEs), S100A12, and high mobility group box chromosomal protein 1 has been associated with joint inflammation in rheumatoid arthritis (RA). This study was undertaken to determine the induction of the receptor for these proteins, termed receptor for AGEs (RAGE), in synovial tissue (ST) macrophages from RA patients.

Methods: RAGE and CD68 expression in ST were determined by 2-color immunofluorescence labeling.

Resistance to IL-10 inhibition of interferon gamma production and expression of suppressor of cytokine signaling 1 in CD4+ T cells from patients with rheumatoid arthritis.

IL-10 has been shown to block the antigen-specific T-cell cytokine response by inhibiting the CD28 signaling pathway. We found that peripheral blood CD4+ T cells from patients with active rheumatoid arthritis (RA) were able to produce greater amounts of interferon gamma after CD3 and CD28 costimulation in the presence of 1 ng/ml IL-10 than were normal control CD4+ T cells, although their surface expression of the type 1 IL-10 receptor was increased. The phosphorylation of signal transducer and activator of transcription 3 was sustained in both blood and synovial tissue CD4+ T cells of RA, but it was not augmented by the presence of 1 ng/ml IL-10.

Histone deacetylase inhibitor suppression of autoantibody-mediated arthritis in mice via regulation of p16INK4a and p21(WAF1/Cip1) expression.

Objective: To examine whether depsipeptide (FK228), a histone deacetylase (HDA) inhibitor, has inhibitory effects on the proliferation of synovial fibroblasts from rheumatoid arthritis (RA) patients, and to examine the effects of systemic administration of FK228 in an animal model of arthritis.

Methods: Autoantibody-mediated arthritis (AMA) was induced in 19 male DBA/1 mice (6-7 weeks old); 10 of them were treated by intravenous administration of FK228 (2.5 mg/kg), and 9 were used as controls.

Expression of interleukin 12 receptor (IL-12R) and IL-18R on CD4+ T cells from patients with rheumatoid arthritis.

Objective: Interleukin 12 (IL-12) and IL-18 synergistically induce interferon-gamma (IFN-gamma) production by T cell infiltrates in rheumatoid arthritis (RA). To investigate this synergism, we examined the expression and regulation of IL-12 receptor (IL-12R) and IL-18R on peripheral blood (PB) and synovial tissue (ST) CD4+ T cells from patients with RA.

Methods: The mRNA and cell surface expression of IL-12R and IL-18R in CD4+ T cells were determined by reverse transcriptase-polymerase chain reaction and flow cytometry, respectively.

Pathophysiological functions of CD30+ CD4+ T cells in rheumatoid arthritis.

High levels of soluble CD30 (sCD30) were detected in the serum and synovial fluid of patients with rheumatoid arthritis (RA), indicating the involvement of CD30+ T cells in the pathogenesis. We investigated the induction of CD30 and its functions in CD4+T cells from patients with established RA (disease duration >_2 years). CD4+ T cells from both the peripheral blood (PB) and synovial tissue (ST) of RA patients expressed surface CD30 when stimulated with anti-CD3 antibody (Ab) and anti-CD28 Ab, but their CD30 induction was slower and weaker compared with PB CD4+ T cells of healthy controls (HC).

[Adult onset Still's disease (AOSD) treated with a combination of prednisolone, cyclosporin A, and methotrexate].

A 58-year-old Japanese woman developed spiking fever, polyarthralgia and hepatosplenomegaly, with highly elevated levels of c-creactive protein (CRP) and ferrtin, and elevated erythrocyte sedimentation rate (ESR). The AOSD was diagnosed according to the Yamaguchi-criteria of 1992. She was first treated with a combination of prednisolone (20 mg/day) and oral methotrexate (MTX) (7.