<h3>Background</h3> One-third of rheumatoid arthritis (RA) patients treated with biological therapy show lack response. The use predictive biomarkers to identify responders treatment may provide guidance in optimising strategies and reduce unnecessary side effects costs. <h3>Objective</h3> To test the ability myeloid-related proteins (MRP)8/14 protein complexes, an endogenous TLR-4 receptor agonist, predict monitor response biologics RA patients. <h3>Methods</h3> 170 adalimumab (n=86),...

BackgroundHeart rate variability (HRV) is a validated method to establish autonomic nervous system (ANS) activity. Rheumatoid arthritis (RA) accompanied by ANS imbalance. We hypothesized that dysfunction may precede the development of RA, which would suggest it plays role in its etiopathogenesis.MethodsFirst, we assessed HRV parameters supine (resting) and upright (active) position healthy subjects (HS, n = 20), individuals at risk developing (AR subjects, 50) RA patients (RA, 20). Next,...

Background The aim of this study was to provide more insight into the question as why blockade CCR1, CCR2, and CCR5 may have failed in clinical trials rheumatoid arthritis (RA) patients, using an vitro monocyte migration system model. Methodology/Principal Findings Monocytes from healthy donors (HD; n = 8) or RA patients (for CCR2 antibody 8; for CCR1 13) were isolated peripheral blood pre-incubated with different concentrations either anti-CCR1, anti-CCR2, anti-CCR5 blocking antibodies (or...

Objective Innate lymphoid cells (ILCs) are emerging mediators of immunity, and accumulation inflammatory ILC populations can occur in inflammatory‐mediated conditions. Since early lymph node (LN) activation has been shown rheumatoid arthritis (RA), we aimed to investigate the frequency distribution ILCs LN biopsy specimens obtained during earliest phases RA. Methods Twelve patients with RA, 12 individuals IgM factor and/or anti–citrullinated protein antibodies without (RA risk group), 7...

Introduction Previous studies have shown increased expression of stromal markers in synovial tissue (ST) patients with established rheumatoid arthritis (RA). Here, ST early relationship to diagnosis and prognostic outcome was studied. Methods from 56 included two different cohorts 7 non-inflammatory controls analysed using immunofluorescence detect CD55, CD248, fibroblast activation protein (FAP) podoplanin. Diagnostic classification (gout, psoriatic arthritis, unclassified (UA), parvovirus...

Objectives We have previously shown that overweight may increase the risk of developing rheumatoid arthritis (RA) in autoantibody positive individuals. Adipose tissue could contribute to development RA by production various bioactive peptides. Therefore, we examined levels adipokines serum and synovial subjects at RA. Methods Fifty-one individuals for immunoglobulin M factor (IgM-RF) and/or anti-citrullinated protein antibodies (ACPA), without arthritis, were included this prospective study....

Objectives Measurement of MRP8/14 serum levels has shown potential in predicting clinical response to different biological agents rheumatoid arthritis (RA). We aimed develop a treatment algorithm based on prediction score using measurements and parameters predictive for agents. Methods Baseline were measured 170 patients starting with infliximab, adalimumab or rituximab. used logistic regression analysis at 16 weeks. along variables baseline investigated. also investigated how the effect was...

The nuclear factor-κB (NF-κB) family of transcription factors is strongly involved in synovial inflammation. We have previously shown that NF-κB-inducing kinase (NIK) a key regulator inflammation-induced angiogenesis rheumatoid arthritis (RA) tissue (ST). Here, we investigated NIK expression patients with early and autoantibody-positive individuals at risk developing RA.ST biopsies were obtained by arthroscopy from 154 (duration < 1 yr) various diagnoses 54 IgM factor-positive and/or...

Although many studies are focused on auto‐reactive CD4 + T cells, the precise role of CD8 cells in autoimmunity is poorly understood. The objective this study to provide more insight into phenotype and function during development autoimmune disease by studying human lymph‐node biopsies peripheral blood obtained earliest phases rheumatoid arthritis (RA). Here, we show that lymphoid pro‐inflammatory exhibit a less‐responsive already compared with healthy individuals. We found an increase...

To identify molecular changes in synovium before arthritis development individuals at risk of developing rheumatoid (RA).We included 67 IgM factor and/or anti-citrullinated protein antibody positive with arthralgia but without arthritis. Synovial biopsies were collected after which prospectively followed for least 2 years during 17 developed An exploratory genome-wide transcriptional profiling study was performed 13 preselected to transcripts associated (n = 6). Findings validated using...

The change in number of CD68-positive sublining macrophages serial synovial biopsies has been successfully used to discriminate on the group level between effective and ineffective treatment during early drug development rheumatoid arthritis (RA) patients. Measurement a soluble biomarker would clearly have practical advantages. Therefore, we investigated sensitivity myeloid related protein (MRP)8/14 serum.139 RA patients who received known biologics (infliximab, adalimumab rituximab) 28...

Abstract Infections are implicated in autoimmunity. Autoantibodies produced lymphoid tissue where lymph node stromal cells (LNSCs) regulate lymphocyte function. can alter the interaction between LNSCs and lymphocytes resulting defective immune responses. In rheumatoid arthritis (RA) autoantibody production precedes clinical disease allowing identification of at risk individuals. We investigated ability human derived from RA, RA-risk healthy individuals to sense respond pathogens. Human...

<h3>Background</h3> Previous work has suggested subtle infiltration of synovial T cells¹ in the absence overt inflammation² individuals at risk developing rheumatoid arthritis (RA). <h3>Objectives</h3> To study molecular changes synovium preceding development preclinical RA. <h3>Methods</h3> We included sixty-seven who were IgM factor (RF) and/or anti-citrullinated protein antibody (ACPA) positive and without any evidence arthritis. All underwent mini-arthroscopic...

<h3>Background and Objective</h3> Rheumatoid arthritis (RA) is an autoimmune disease with unknown etiology. Immune activation in peripheral lymphoid tissues seems to precede synovial tissue inflammation. The stromal compartment of lymph nodes crucial for the induction adaption immune responses. Recent murine studies have implicated a role node cells (LNSCs) tolerance due their expression Aire. In thymus regulator Aire main transcription factor regulating T cell central by driving...

<h3>Background</h3> Biological therapy has dramatically improved the treatment of rheumatoid arthritis (RA). One-third patients however show a lack clinical response to this treatment. The use robust predictive markers identify individuals who are likely respond biological treatments may provide guidance in optimizing strategies and lead lower costs. <h3>Objectives</h3> To test ability MRP8/14 serum complexes, major granulocyte monocyte protein associated with inflammation RA¹,...

Abstract Background Previous work has shown subtle infiltration of synovial T cells in the absence overt inflammation individuals at risk developing rheumatoid arthritis (RA). Objective To study molecular changes synovium preceding development individuals. Materials and methods We included sixty-seven with arthralgia who were IgM factor (RF) and/or anti-citrullinated protein antibody (ACPA) positive without any evidence arthritis. All underwent mini-arthroscopic tissue sampling a knee joint...

<h3>Background and Objective</h3> Recently, we showed increased T cell activation in lymph node biopsies of early rheumatoid arthritis (RA) patients. We hypothesise that different T-cell subsets are involved the regulation immune responses during earliest phases RA. <h3>Materials Methods</h3> included 11individuals with arthralgia without any evidence who were positive for IgM factor (IgM-RF) and/or anti-citrullinated protein antibodies (ACPA; RA risk group), 18 DMARD naïve patients...

<h3>Background</h3> Recent data suggest RA may originate from an autoimmune response in inflamed mucosa. is associated with gingival and airway inflammation. Porphyroma gingivalis, a bacterium causing gingivitis, has been implicated ACPA formation. Furthermore, of the IgA class, main secreted mucosal antibody, precede arthritis by years proportion patients. When aiming to prevent it central importance understand source regulation autoantibody production pre-clinical RA. <h3>Objectives</h3>...

<h3>Background</h3> Rheumatoid arthritis (RA) is an autoimmune disease with unknown etiology. Immune activation in peripheral lymphoid tissues seems to precede synovial tissue inflammation. The stromal compartment of lymph nodes crucial for the induction and shaping immune responses. Recent murine studies have implicated a role node cells (LNSCs) tolerance due their expression Aire. In thymus regulator Aire main transcription factor regulating T cell central by driving tissue-restricted...