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ID PMID Title PublicationDate abstract
27707730 Discordance between tender and swollen joint count as well as patient's and evaluator's gl 2017 Apr OBJECTIVE: To investigate the predictive value of discordance between (1) tender and swollen joint count and (2) patient's and evaluator's global assessment on remission in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA). METHODS: From the prospective, multicentre Norwegian-Disease-Modifying Antirheumatic Drug study, we included patients with RA and PsA starting first-time tumour necrosis factor inhibitors and DMARD-naïve patients starting methotrexate between 2000 and 2012. The predictive value of ΔTSJ (tender minus swollen joint counts) and ΔPEG (patient's minus evaluator's global assessment) on remission was explored in prespecified logistic regression models adjusted for age, sex, disease duration and smoking. RESULTS: A total of 2735 patients with RA and 1236 patients with PsA were included (mean (SD) age 55.0 (13.5)/48.3 (12.4) years, median(range) disease duration 0.7 (0.0-58.0)/1.3 (0.0-48.3) years, 69.7/48.4% females). Baseline ΔTSJ/ΔPEG reduced the likelihood of achieving DAS28<2.6, SDAI≤3.3, CDAI≤2.8, ACR/EULAR Boolean and DAPSA<4 remission after 3 and 6 months in RA (OR 0.95-0.97, p<0.001/OR 0.96-0.99, p≤0.01) and PsA (OR 0.91-0.94, p≤0.004/OR 0.89-0.99, p≤0.002), except for ΔPEG and 6-month DAS28 remission in PsA. CONCLUSIONS: Discordance between patient's and physician's evaluation of disease activity reflected through ΔTSJ and partly ΔPEG may reduce likelihood of remission in RA and PsA. The findings are relevant for use of the treat-to-target strategy in individual patients.
24131486 Induction of proliferation and pro-inflammatory cytokine production in rheumatoid arthriti 2017 Sep OBJECTIVE: To analyze proliferation and pro-inflammatory cytokine production of peripheral blood mononuclear cells (PBMC) from rheumatoid arthritis (RA) patients following stimulation with a purified chondrocyte membrane-associated autoantigen (CH65). METHODS: CH65 was highly purified from bovine chondrocyte membranes by solubilization and ion exchange chromatography. PBMC of RA patients (n = 37; 28 seropositive, nine seronegative) and non-arthritic donors (n = 20) were isolated by ficoll centrifugation and used in cell proliferation assays. The levels of interleukin (IL)-1, tumo necrosis factor (TNF) and IL-6 produced after stimulation with CH65 were determined by enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using Mann-Whitney U-test and Spearman rank test and the software SPSS 13.0(TM) (SPSS Inc.; Chicago, IL, USA). RESULTS: Peripheral blood mononuclear cells exhibited a strong proliferative response to purified CH65 in approximately 50% of the RA patients (seropositive > seronegative), with a maximum reactivity at 0.15 or 0.30 μg/mL culture medium. In contrast, PBMC from normal donors did not show a proliferative response to CH65 at any dose. The proliferative response in RA patients peaked at days 7-9 and returned to control levels at day 13, indicating an antigen-driven process. CH65-stimulated RA PBMC produced moderate to high amounts of IL-1, TNF and IL-6. This was comparable to the response after exposure to isolated whole chondrocyte membranes or purified collagen type II. CONCLUSION: These results demonstrate a significant cellular immune response to CH65 protein in RA patients. Given the high similarity between bovine and human CH65, the results suggest a pathogenetic involvement of this molecule as a cartilage-specific potential target autoantigen in RA.
29185958 Are rheumatologists adhering to the concepts window of opportunity and treat-to-target? Ea 2018 May OBJECTIVES: To analyse changes over time in the treatment with disease modifying anti-rheumatic drugs and biological therapies prescribed to patients from an early arthritis register and whether these changes had an impact on their outcome. METHODS: This was a longitudinal retrospective 2-year study based on data collected in the PEARL study. The population was clustered in three groups depending on year of symptoms onset (2000-2004, 2005-2009, 2010-2014). Intensity of disease-modifying anti-rheumatic drug treatment was calculated and the percentage of patients receiving biological therapy during the first 2-year follow-up was collected. Disease activity and remission at the end of follow-up, as well as radiological progression were the outcomes analysed. Multivariable analyses were fitted to determine which variables including the three period times were associated with the outcomes. RESULTS: A significant increase in treatment intensity was observed in patients with undifferentiated arthritis, getting closer to that prescribed to patients fulfilling the 1987 RA criteria at the last period studied (2010-2014). This finding was associated with a significantly higher percentage of patients in remission and lower progression of the erosion component of the Sharp van der Heijde score. CONCLUSIONS: During the last 15 years, the treatment of patients with early arthritis in our hospital has been progressively increased and it has been associated with significantly better outcomes.
28105533 Semi-Automated Quantification of Finger Joint Space Narrowing Using Tomosynthesis in Patie 2017 Jun The purpose of the study is to validate the semi-automated method using tomosynthesis images for the assessment of finger joint space narrowing (JSN) in patients with rheumatoid arthritis (RA), by using the semi-quantitative scoring method as the reference standard. Twenty patients (14 females and 6 males) with RA were included in this retrospective study. All patients underwent radiography and tomosynthesis of the bilateral hand and wrist. Two rheumatologists and a radiologist independently scored JSN with two modalities according to the Sharp/van der Heijde score. Two observers independently measured joint space width on tomosynthesis images using an in-house semi-automated method. More joints with JSN were revealed with tomosynthesis score (243 joints) and the semi-automated method (215 joints) than with radiography (120 joints), and the associations between tomosynthesis scores and radiography scores were demonstrated (P < 0.001). There was significant, negative correlation between measured joint space width and tomosynthesis scores with r = -0.606 (P < 0.001) in metacarpophalangeal joints and r = -0.518 (P < 0.001) in proximal interphalangeal joints. Inter-observer and intra-observer agreement of the semi-automated method using tomosynthesis images was in almost perfect agreement with intra-class correlation coefficient (ICC) values of 0.964 and 0.963, respectively. The semi-automated method using tomosynthesis images provided sensitive, quantitative, and reproducible measurement of finger joint space in patients with RA.
28118521 Brief Report: Treatment of Tumor Necrosis Factor-Transgenic Mice With Anti-Tumor Necrosis 2017 Jun OBJECTIVE: Recent studies have demonstrated that there is an inverse relationship between lymphatic egress and inflammatory arthritis in affected joints. As a model, tumor necrosis factor (TNF)-transgenic mice develop advanced arthritis following draining lymph node (LN) collapse, and loss of lymphatic contractions downstream of inflamed joints. It is unknown if these lymphatic deficits are reversible. This study was undertaken to test the hypothesis that anti-TNF therapy reduces advanced erosive inflammatory arthritis, associated with restoration of lymphatic contractions, repair of damaged lymphatic vessels, and evidence of increased monocyte egress. METHODS: TNF-transgenic mice with advanced arthritis and collapsed popliteal LNs were treated with anti-TNF monoclonal antibody (10 mg/kg weekly) or placebo for 6 weeks, and effects on knee synovitis, lymphatic vessel ultrastructure and function, and popliteal LN cellularity were assessed by ultrasound, histology, transmission electron microscopy (TEM), near-infrared indocyanine green imaging, and flow cytometry. RESULTS: Anti-TNF therapy significantly decreased synovitis (∼5-fold; P < 0.05 versus placebo), restored lymphatic contractions, and significantly increased the number of popliteal LN monocyte/macrophages (∼2-fold; P < 0.05 versus placebo). TEM demonstrated large activated macrophages attached to damaged lymphatic endothelium in mice with early arthritis, extensively damaged lymphatic vessels in placebo-treated mice with advanced arthritis, and rolling leukocytes in repaired lymphatic vessels in mice responsive to anti-TNF therapy. CONCLUSION: These findings support the concept that anti-TNF therapy ameliorates erosive inflammatory arthritis, in part via restoration of lymphatic vessel contractions and potential enhancement of inflammatory cell egress.
29413504 Several high-resolution computed tomography findings associate with survival and clinical 2018 Jan OBJECTIVE: To compare the presence and extent of several high-resolution computed tomography (HRCT) observations in different subtypes of rheumatoid arthritis-related interstitial lung disease (RA-ILD) and to examine associations between radiological findings, hospitalization, age, RA duration, pulmonary function tests (PFT) and survival. MATERIALS AND METHODS: HRCTs from 60 RA-ILD patients were independently evaluated and re-categorized into usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), organizing pneumonia (OP), diffuse alveolar damage (DAD) and unclassified subtypes by two radiologists. The presence and extent, which was reported using a semi-quantitative scoring system, of e.g. reticulation, ground-glass opacity, honeycombing, emphysema, traction bronchiectasis and architectural distortion were further evaluated and compared between the subtypes. Associations between radiological findings and survival were identified with the Kaplan-Meier method and Cox's univariate model. The correlations between radiological findings, hospitalization, age, pack years, RA duration and PFT were calculated using Spearman's correlation coefficient. RESULTS: The extents of reticulation (HR 1.144, p = 0.041), traction bronchiectasis (HR 1.184, p = 0.030), architectural distortion (HR 1.094, p = 0.044) and the presence of pleural fluid (HR 14.969, p < 0.001) were associated with decreased survival. A negative correlation was observed between ground-glass opacity (GGO) and the duration of RA (r = -0.308, p = 0.023). The extents of honeycombing (r = 0.266, p = 0.046), traction bronchiectasis (r = 0.333, p = 0.012) and architectural distortion (r = 0.353, p = 0.007) correlated with hospitalizations due to respiratory reasons. CONCLUSIONS: Many radiological findings associate with the course of the disease of RA-ILD and could potentially be useful when planning the RA treatment or evaluating the risk of death in these patients.
27509834 Bone-density testing interval and transition to osteoporosis in patients with rheumatoid a 2017 Jan The study aims to evaluate the rate of transition to osteoporosis in 360 RA patients and estimate the rescreening intervals of bone mineral density (BMD) testing. Osteoporosis was newly developed in 24.8 % during mean follow-up of 7.4 years. The estimated time of a BMD testing interval was dependent on the baseline T-score in RA patients. INTRODUCTION: Although BMD testing is routinely performed in RA patients, the interval between BMD tests has not been determined. METHODS: We retrospectively recruited 360 consecutive female patients with RA, who underwent repeated BMD testing, with a mean age of 53.7 ± 10.2 years and a mean follow-up duration of 7.4 ± 5.0 years. We stratified the study participants into five groups based on their baseline T-score range. The testing interval was defined as the estimated time for 10 % of patients in each subgroup to transition to osteoporosis. Competing-risk analyses were performed with sensitivity analysis by menopausal status and risk factors for transition to osteoporosis. RESULTS: At baseline, 15 % of screened patients had osteoporosis, and during follow-up, that proportion increased to 24.8 %. The estimated BMD testing interval for 10 % of patients to develop osteoporosis was 9.6 years for those with normal BMD, 7.6 years for those with mild osteopenia, 4.7 years for those with moderate osteopenia, and 2.1 years for those with severe osteopenia. No significant risk factor for transition to osteoporosis was identified in this cohort. CONCLUSIONS: Our data indicate that osteoporosis will develop in less than 10 % of female RA patients during rescreening intervals of approximately 9 years for those with normal bone density at baseline, 7 years for those with mild osteopenia, 4 years for those with moderate osteopenia, and 2 years for those with severe osteopenia at baseline. BMD interval in RA patients could be adjusted according to their baseline BMD T-scores.
29097373 Predictors of revision, prosthetic joint infection and mortality following total hip or to 2018 Feb OBJECTIVES: To investigate predictors of 10-year risk of revision and 1-year risk of prosthetic joint infection (PJI) and death following total hip/total knee arthroplasty (THA/TKA) in (1) patients with rheumatoid arthritis (RA) compared with patients with osteoarthritis (OA); and (2) patients with RA treated with biological disease-modifying antirheumatic drugs (bDMARD) within 90 days preceding surgery compared with non-treated. METHODS: Register-based cohort study using the Danish National Patient Register, the DANBIO rheumatology register (RA-specific confounders and treatment episodes) and the Danish Hip and Knee Arthroplasty Registers. Survival analyses were used to calculate confounder-adjusted sub-HRs (SHR) and HRs. RESULTS: In total, 3913 patients with RA with THA/TKA were compared with 120 499 patients with OA. Patients with RA had decreased risk of revision (SHR 0.71 (0.57-0.89)), but increased risk of PJI (SHR=1.46 (1.13-1.88)) and death (HR=1.25 (1.01-1.55)). In DANBIO, 345 of 1946 patients with RA with THA/TKA had received bDMARD treatment within 90 days preceding surgery. bDMARD-treated patients did not have a statistically significant increased risk of revision (SHR=1.49 (0.65-3.40)), PJI (SHR=1.61 (0.70-3.69)) nor death (HR=0.75 (0.24-2.33)) compared with non-treated. Glucocorticoid exposure (HR=2.87 (1.12-7.34)) and increasing DAS28 (HR=1.49 (1.01-2.20)) were risk factors for mortality. CONCLUSION: Patients with RA had a decreased 10-year risk of revision while the risk of death and PJI was increased compared with patients with OA following THA/TKA. bDMARD exposure was not associated with statistically significant increased risk of neither PJI nor death in this study. Glucocorticoid exposure and increased disease activity were associated with an increased risk of death.
28009092 Arthritis management in primary care - A study of physiotherapists' current practice, educ 2017 Dec BACKGROUND: With an increasing number of patients with osteoarthritis (OA) and rheumatoid arthritis (RA) in primary care, our aim was to investigate arthritis-related practice in physiotherapy and to study adherence to evidence-based care. METHODS: Seventy physiotherapists (PTs) working in primary care were emailed a questionnaire to investigate current practice and the number of roles assumed by PTs, the degree of confidence, educational needs and adherence to national guidelines in managing patients with OA or RA. Interventions supported by national guidelines were compared with reports of treatment modalities in the questionnaire. RESULTS: Sixty-four (91%) PTs responded, and they reported a higher degree of confidence in assessment, treatment and education of patients with OA than for those with RA (p < 0.001). The total number of roles assumed by the PTs was higher in the management of OA than for RA (p < 0.001). PTs who assumed a greater number of roles also reported a stronger degree of confidence in assessing OA (p = 0.036). Those who assumed fewer roles also reported less confidence in RA treatment (p = 0.045). Recommendations in the guidelines were followed by the majority of PTs for eight of 11 treatment modalities in OA and for six of six in RA. CONCLUSIONS: PTs reported a lower degree of confidence and the assumption of fewer roles in managing patients with RA compared with OA. There was good adherence to the national guidelines for almost all the treatment modalities listed. Even so, the results indicate a need for education, especially in chronic inflammatory arthritis care.
28243799 Anti-citrullinated protein antibodies are associated with decreased bone mineral density: 2017 May Since the previous studies showed that anti-citrullinated protein antibodies (ACPA) can induce osteoclasts differentiation and activation, even before arthritis onset, the aim of our study was to determine whether ACPA-positivity is associated with lower bone mineral density (BMD) at baseline visit of a register of early arthritis (EA) patients. The study population comprised 578 patients (80% females) from our EA clinic with a median disease duration, 5.1 months (p25-p75: 6-8); median age, 53.6 years (41.9-66.1), 38% ACPA-positive, and 55% fulfilling 2010 criteria for rheumatoid arthritis. BMD was measured using dual X-ray absorptiometry at lumbar spine, hip, and metacarpophalangeal (MCP) joints of the non-dominant hand to evaluate both systemic and juxta-articular bone mass. ACPA titers were determined through enzyme immunoassay. The effect of ACPA on BMD was analyzed using multivariable analysis based on generalized linear models adjusted for various confounders. ACPA-positive patients showed lower bone mass at lumbar spine and hip, but no differences were observed at MCP joints compared to ACPA-negative patients. However, ACPA-positive patients displayed higher disease activity and disability than ACPA-negative patients. After adjustment for gender, age, body mass index, and other bone-related variables, the presence of ACPA remained significantly associated with lower BMD at the lumbar spine, femoral neck, and hip but not at MCP joints. Disease activity was not associated with baseline bone mass. Our data reinforce the previous preclinical findings suggesting that the systemic bone loss detected at the initial phases of early ACPA-positive arthritis is independent of inflammatory status and, therefore, could be mediated by ACPA.
28711880 The Relationship Between Synovial Pathobiology and Magnetic Resonance Imaging Abnormalitie 2017 Sep OBJECTIVE: Magnetic resonance imaging (MRI) has been increasingly recognized as a critical tool for the assessment of patients with rheumatoid arthritis (RA) and is able to reliably identify synovitis, bone marrow edema, bone erosion, and joint space narrowing (JSN)/cartilage loss. Understanding the exact relationship between each MRI feature and local synovial pathobiology is critical to dissect disease pathogenesis as well as develop future predictive models. METHODS: A systematic review was performed of the current published literature examining the relationship between MRI abnormalities and synovial pathobiology in patients with RA. RESULTS: Eighteen studies were identified; most focused on validation of MRI as a tool to detect and quantify synovitis, with a significant relationship demonstrated. Additionally, from the limited data available, a critical role seems likely for synovial pathways, at least in driving joint damage. However, there was a lack of data examining the relationship between synovial pathobiology and bone marrow abnormalities and JSN. CONCLUSION: Although understanding the interrelationship of these disease biomarkers offers the potential to enhance the predictive validity of modern imaging with concomitant synovial pathobiological analysis, further studies integrating MRI with synovial tissue analysis in well-controlled cohorts at distinct disease stages before and after therapeutic intervention are required to achieve this.
28371410 New genes associated with rheumatoid arthritis identified by gene expression profiling. 2017 Jun In this study, we aimed to find new genes associated with rheumatoid arthritis (RA) so that more comprehensive genes would be used for monitoring and/or diagnosing patients. Illumina digital gene expression profiling was applied in two sample types - peripheral blood mononuclear cells (PBMCs) and synovial cells to compare the gene expression pattern between 17 patients with RA and three control groups (six osteoarthritis patients, three ankylosing spondylitis patients and 17 healthy controls). Bioinformatics was performed on pathway analysis and protein-protein interaction networks. Four novel genes from PBMCs - DHRS3, TTC38, SAP30BP and LPIN2 - were found to be associated with RA and further confirmed through quantitative real-time polymerase chain reaction. Five new differentially expressed genes (EPYC, LIFR, GLDN, TADA3 and ZNRF3) found in synovial cells were not confirmed. Pathway analyses revealed 10 significantly enriched pathways, and a protein-protein interaction network analysis showed that four novel PBMC-derived genes were connected to previously reported genes by four intermediate genes. Therefore, we proposed that four newly identified PBMC-derived genes could be integrated with previously reported RA-associated genes to monitor and/or diagnose RA.
28733141 Gastrin-releasing peptide and its receptor increase arthritis fibroblast-like synoviocytes 2017 Sep Rheumatoid arthritis (RA) is an autoimmune disease that leads to joint destruction. The fibroblast-like synoviocytes (FLS) has a central role on the disease pathophysiology. The present study aimed to examine the role of gastrin-releasing peptide (GRP) and its receptor (GRPR) on invasive behavior of mice fibroblast-like synoviocytes (FLS), as well as to evaluate GRP-induced signaling on PI3K/AKT pathway. The expression of GRPR in FLS was investigated by immunocytochemistry, western blot (WB) and qRT-PCR. The proliferation and invasion were assessed by SRB and matrigel-transwell assay after treatment with GRP and/or RC-3095 (GRPR antagonist), and/or Ly294002 (inhibitor of PI3K/AKT pathway). Finally, AKT phosphorylation was assessed by WB. GRPR protein was detected in FLS and the exposure to GRP increased FLS invasion by nearly two-fold, compared with untreated cells (p<0.05), while RC-3095 reversed that effect (p<0.001). GRP also increased phosphorylated AKT expression in FLS. When Ly294002 was added with GRP, it prevented the GRP-induced increased cell invasiveness (p<0.001). These data suggest that GRPR expression in FLS and that exogenous GRP are able to activate FLS invasion. This effect occurs at least in part through the AKT activation. Therefore, understanding of the GRP/GRPR pathway could be relevant in the development of FLS-targeted therapy for RA.
28384116 YKL-40 and cytokines - a New Diagnostic Constellation in Rheumatoid Arthritis? 2017 Mar 1 BACKGROUND: Rheumatoid arthritis (RA) causes chronic inflammation and alteration of articular tissue and joints. The pathogenesis of the disease remains unclear although it is known that proinflammatory cytokines play a major role in its induction. YKL-40 is a chitinase-like glycoprotein produced by activated macrophages, neutrophils, arthritic chondrocytes and cancer cells. It has been shown that YKL-40 is implicated in tissue remodeling, angiogenesis and inflammation. AIM: to investigate serum and synovial YKL-40 levels in relation to IL-1β, TNF-α, and IL-6 in RA patients. MATERIALS AND METHODS: Serum and synovial concentrations of YKL-40, TNF-α, IL- 6, and IL-1β were determined by ELISA in 39 patients (mean age 53.18 ± 16.54 yrs) with active RA. RESULTS: Serum YKL-40 levels were increased in all patients. The highest levels were found in synovial fluid (P<0.01). Our study showed a strong association between serum and synovial levels of YKL-40 and serum TNF-α and IL-1 β (P<0.05). CONCLUSION: This is the first study finding a significant correlation between serum TNF-α and IL-1β and YKL-40 in active RA. We suggest that these molecules together might play a dominant role in the pathogenesis and disease activity and could possibly serve as a new diagnostic constellation in rheumatoid arthritis.
28526072 Differences in serum and synovial CD4+ T cells and cytokine profiles to stratify patients 2017 May 19 BACKGROUND: The aim was to investigate CD4(+)T-cell subsets, immune cells and their cytokine profiles in blood and synovial compartments in rheumatoid arthritis (RA) and inflammatory osteoarthritis (OA) to define specific immune signatures. METHODS: Peripheral blood, synovial fluid (SF) and synovial membranes (SM) of RA and OA patients were analyzed. CD4(+)T-cell subset frequencies were determined by flow cytometry, and cytokine concentrations in serum and SF were measured by ELISA. RESULTS: In peripheral blood, OA patients had altered frequencies of regulatory T-cell subsets, and higher frequencies of Th17 and of Th1/17 cells than RA patients. In the synovial compartment of OA patients, conventional Th17 cells were largely excluded, while Th1/17 cells were enriched and more frequent than in RA patients. Conversely, in the synovial compartment of RA patients, regulatory T cells and Tfh cells were enriched and more frequent then in OA patients. IL-17 and Blys were increased both in serum and SF of RA patients, and correlated with autoantibodies and disease activity. Notably, Blys levels were already significantly elevated in RA patients with low disease activity score in 28 joints (DAS28) and without autoantibody positivity. CONCLUSIONS: Although patients with inflammatory OA have immune activation in the synovial compartment, they display different T-cell subset frequencies and cytokine profiles. Soluble mediators such as Blys might help to discriminate mild clinical forms of RA from inflammatory OA particularly at the onset of the disease.
28681656 Detection of synovial inflammation in rheumatic diseases using superb microvascular imagin 2018 Mar AIM: Superb microvascular imaging (SMI), a novel ultrasonography, is based on the sensitivity of Doppler technology. This study evaluated power Doppler (PD) ultrasound signals in patients with rheumatic disease using SMI and conventional PD imaging (cPDI) and compared the correlations of these signals to clinical assessments. METHODS: Thirty-nine patients with rheumatic disease (27 rheumatoid arthritis [RA] and 12 non-RA) were enrolled. We investigated SMI and cPDI signals in 26 joints using an Aplio 300. Individual scores were summed to calculate total SMI and cPDI scores. RESULTS: Total SMI scores were significantly higher than total cPDI scores in patients with RA, but not in those with the non-RA disease. Total SMI score was associated with serum levels of C-reactive protein (CRP) and matrix metalloproteinase-3; disease activity score 28-CRP and health assessment questionnaire disability index scores, and SMI were more sensitive to detect active synovitis than cPDI in RA patients. Among the joint regions, the wrists and metacarpophalangeal joints were more sensitive to the detection of synovial inflammation using SMI in patients with RA. CONCLUSION: SMI was more sensitive in detecting synovial inflammation than cPDI in patients with RA. SMI could be a potentially useful imaging modality for accurately diagnosing and monitoring the disease activity of RA.
27718235 The soluble cytoplasmic tail of CD45 (ct-CD45) in human plasma contributes to keep T cells 2017 Jan The cytoplasmic tail of CD45 (ct-CD45) is proteolytically cleaved and released upon activation of human phagocytes. It acts on T cells as an inhibitory, cytokine-like factor in vitro. Here, we show that ct-CD45 is abundant in human peripheral blood plasma from healthy adults compared with plasma derived from umbilical cord blood and plasma from patients with rheumatoid arthritis or systemic lupus erythematosus. Plasma depleted of ct-CD45 enhanced T-cell proliferation, while addition of exogenous ct-CD45 protein inhibited proliferation and reduced cytokine production of human T lymphocytes in response to TCR signaling. Inhibition of T-cell proliferation by ct-CD45 was overcome by costimulation via CD28. T-cell activation in the presence of ct-CD45 was associated with an upregulation of the quiescence factors Schlafen family member 12 (SLFN12) and Krueppel-like factor 2 (KLF2) as well as of the cyclin-dependent kinase (CDK) inhibitor p27kip1. In contrast, positive regulators of the cell cycle such as cyclin D2 and D3 as well as CDK2 and CDK4 were found to be downregulated in response to ct-CD45. In summary, we demonstrate that ct-CD45 is present in human plasma and sets the threshold of T-cell activation.
28424905 Association of STAT4 rs7574865 and PTPN22 rs2476601 polymorphisms with rheumatoid arthriti 2017 Sep The aim of this study was to investigate association of protein tyrosine phosphatase non-receptor type 22 (PTPN22) rs2476601 and signal transducer and activator of transcription 4 (STAT4) rs7574865 polymorphisms with rheumatoid arthritis (RA) susceptibility and to assess potential association with the status of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies, serum neopterin, and disease activity. RF, anti-CCP antibodies, and neopterin were assayed in serum of 100 unrelated RA patients and 114 controls. STAT4 rs7574865 G/T and PTPN22 rs2476601 C/T polymorphisms were genotyped by the TaqMan allelic discrimination method. The frequency of STAT4 variant allele was significantly higher in RA patients than in controls (p = 0.01), while the variant allele of PTPN22 was identified in only two RA patients, in a heterozygous form and in none of control subjects. The frequency of STAT4 variant allele carrier genotypes (GT+TT) was significantly higher among RA patients than in controls (43.7 vs. 10.5%, p = 0.02) and associated with RA under additive and dominant models. The frequency of RF and anti-CCP positivity was significantly higher among RA patients carrying T allele genotypes compared to patients carrying wild genotype (P = 0.02 and 0.04, respectively). No significant associations between STAT4 variant and serum neopterin or disease activity parameters were identified. Our study confirmed the association of STAT4 rs7574865 polymorphism with RA and was the first to indicate an association with RF and anti-CCP antibodies positivity. We also found PTPN22 rs2476601 has no role in susceptibility to RA in Egyptian patients.
27790752 Increased circulating anti-α6-integrin autoantibodies in psoriasis and psoriatic arthriti 2017 Apr In psoriatic skin, laminin integrity is altered, which could lead to insufficient laminin integrin interactions, leaving the α6-integrin exposed and possibly accessible for autoantibody production. Therefore we investigated the presence of anti-α6-integrin autoantibodies in the serum of patients with psoriasis vulgaris (Ps), psoriatic arthritis (PsA) and rheumatoid arthritis (RA) in comparison with healthy donors. The level of circulating anti-α6-integrin antibodies was determined by enzyme-linked immunoassay using α6-integrin fragments. Antibodies against at least one recombinant fragment were found in approximately 30% of Ps and PsA patients. In contrast, in RA patients, the frequency of antibodies was similar to healthy controls. Our study shows the presence of anti-α6-integrin antibodies in Ps and PsA but not in RA, which could indicate ongoing abnormal processes in the skin. Anti-α6-integrin autoantibodies may contribute to the formation of micro-wounds in the skin and to the characteristic wound-healing phenotype in psoriasis.
28259649 Role of the liver X receptors in skin physiology: Putative pharmacological targets in huma 2017 Oct Liver X receptors (LXRs) are members of the nuclear receptor superfamily that have been shown to regulate various physiological functions such as lipid metabolism and cholesterol homeostasis. Concordant reports have elicited the possibility to target them to cure many human diseases including arteriosclerosis, cancer, arthritis, and diabetes. The high relevance of modulating LXR activities to treat numerous skin diseases, mainly those with exacerbated inflammation processes, contrasts with the lack of approved therapeutic use. This review makes an assessment to sum up the findings regarding the physiological roles of LXRs in skin and help progress towards the therapeutic and safe management of their activities. It focuses on the possible pharmacological targeting of LXRs to cure or prevent selected skin diseases.