Risk of cardiovascular comorbidities before and after the onset of rheumatic diseases.

Objectives: To elucidate the risk and temporal relationship of cardiovascular (CV) comorbidities in rheumatic diseases.

Methods: Patients in the FinnGen study diagnosed between 2000 and 2014 with seropositive (n = 2368) or seronegative (n = 916) rheumatoid arthritis (RA), ankylosing spondylitis (AS, n = 715), psoriatic arthritis (PsA, n = 923), systemic lupus erythematosus (SLE, n = 190), primary Sjogren's syndrome (pSS, n = 412) or gout (n = 2034) were identified from healthcare registries. Each patient was matched based on age, sex, and birth region with twenty controls without any rheumatic conditions.

Tofacitinib treatment modulates the levels of several inflammation-related plasma proteins in rheumatoid arthritis and baseline levels of soluble biomarkers associate with the treatment response.

The data on the effects of tofacitinib on soluble proteins in patients with rheumatoid arthritis (RA) is currently very limited. We analyzed how tofacitinib treatment and thus inhibition of the Janus kinase-signal transducer and activation of transcription pathway affects the in vivo levels of inflammation-related plasma proteins in RA patients. In this study, 16 patients with active RA [28-joint disease activity score (DAS28) >3.

Gorham-Stout disease with life-threatening pleural effusion treated with a pleuro-peritoneal shunt: a case report.

Summary: Gorham-Stout disease (GSD) is a rare bone disease characterized by massive osteolysis and lymphatic proliferation. The origin of the condition is unknown, and no established treatment protocol exists. Massive pleural effusion is a frequent complication of GSD in the thoracic region.

The validity of rheumatoid arthritis diagnoses in Finnish biobanks.

Objective: The aim of this study was to determine the validity of rheumatoid arthritis (RA) diagnoses in patients participating in Finnish biobanks.

Method: We reviewed the electronic medical records of 500 Finnish biobank participants: 125 patients with at least one visit with a diagnosis of seropositive RA, 125 patients with at least one visit with a diagnosis of seronegative RA, and 250 age- and gender-matched controls. The patients were chosen from five different biobank hospitals in Finland.

Tofacitinib Suppresses Several JAK-STAT Pathways in Rheumatoid Arthritis and Baseline Signaling Profile Associates With Treatment Response.

Objective: Current knowledge on the actions of tofacitinib on cytokine signaling pathways in rheumatoid arthritis (RA) is based on studies. Our study is the first to examine the effects of tofacitinib treatment on Janus kinase (JAK) - signal transducer and activator of transcription (STAT) pathways in patients with RA.

Methods: Sixteen patients with active RA, despite treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), received tofacitinib 5 mg twice daily for three months.

Mutation Is Associated with Increased STAT1 and STAT5 Activation in Two Family Members with Inflammatory Conditions and Lymphopenia.

Interferon regulatory factor 2 binding protein 2 (IRF2BP2) is a transcriptional coregulator that has an important role in the regulation of the immune response. IRF2BP2 has been associated with the Janus kinase (JAK)-signal transducers and activators of transcription (STAT) pathway, but its exact role remains elusive. Here, we identified a novel clinical variant, c.

Increased expression of the proprotein convertase enzyme FURIN in rheumatoid arthritis.

Objective: FURIN is a proprotein convertase enzyme that inhibits the proinflammatory function of T cells and myeloid cells. Elevated FURIN expression levels have been reported in immune-mediated diseases, such as primary Sjögren's syndrome. Here, we investigated the levels of FURIN in peripheral blood (PB) and synovial fluid (SF) leucocytes from patients with rheumatoid arthritis (RA).

Proprotein convertase enzyme FURIN is upregulated in primary Sjögren's syndrome.

Objectives: The proprotein convertase enzyme FURIN is a critical regulator of the anti-inflammatory TGFβ-1 cytokine and peripheral immune tolerance. In T cells, FURIN is co-regulated with IFN-γ and thus highly expressed in T helper 1 type cells. Previous studies have demonstrated that FURIN is upregulated in inflammatory conditions, including atherosclerosis, rheumatoid arthritis and systemic lupus erythematosus.

Three out of four disease-modifying anti-rheumatic drug-naïve rheumatoid arthritis patients meet 28-joint Disease Activity Score remission at 12 months: results from the FIN-ERA cohort.

Objective: To assess what proportion of patients with disease-modifying anti-rheumatic drug (DMARD)-naïve early rheumatoid arthritis (ERA) reach 28-joint Disease Activity Score (DAS28) remission over 1 year, and remission variability across clinics in Finland.

Method: Patients with DMARD-naïve newly diagnosed inflammatory arthritis were recruited. The proportion of patients in 28-joint Disease Activity Score with three variables (DAS28-3) remission was compared across sites.

Efficacy and effectiveness of tumour necrosis factor inhibitors in the treatment of rheumatoid arthritis in randomized controlled trials and routine clinical practice.

Objective: Efficacy of TNF inhibitors in the treatment of RA assessed in randomized controlled trials (RCTs) may not be fully comparable to routine care owing to the stringent inclusion criteria. The objective of this study was to observe the effectiveness of TNF inhibitors in real-world patients and assess the patients' potential eligibility for the RCTs.

Methods: RA patients starting a TNF-inhibitor treatment between 2004 and 2014 were identified from the National Register for Biologic Treatment in Finland, which is a longitudinal observational cohort study.

Drug survival on tumour necrosis factor inhibitors in patients with rheumatoid arthritis in Finland.

Objective: A systematic review found that an average of 27% of rheumatoid arthritis (RA) patients using tumour necrosis factor (TNF) inhibitors discontinue their treatment within 1 year. The aim of this study was to assess drug survival on TNF inhibitors among patients with RA.

Methods: Patients were identified from the National Register for Biologic Treatment in Finland (ROB-FIN), which is a longitudinal cohort study established to monitor the effectiveness and safety of biologic drugs in rheumatic diseases.

[Exemplary cases of individualization of biological therapy].

The use of biological drugs consisting of large molecules has in recent years expanded to new indications and new specialties. These drugs are most commonly proteins possessing the structure of an antibody or a receptor, and treatment with them is significantly more expensive than that carried out with conventional small molecule drugs. Determination of drug levels and emerging antibodies form the basis of individualization.

Cytokine-induced STAT1 activation is increased in patients with primary Sjögren's syndrome.

Limited data are available regarding the intracellular responses to different cytokines in primary Sjögren's syndrome (pSS). We studied the signal transducer and activator of transcription (STAT) activation profile in response to cytokine stimulations in peripheral blood mononuclear cells (PBMCs) from pSS patients by multicolor flow cytometry. The expression of the suppressors of cytokine signaling (SOCS), and interferon (IFN)-γ target genes in PBMCs was studied using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR).

STAT-5 is activated constitutively in T cells, B cells and monocytes from patients with primary Sjögren's syndrome.

The expression and phosphorylation of signal transducer and activator of transcription-1 (STAT-1) have been shown to be markedly increased in the salivary gland epithelial cells of patients with primary Sjögren's syndrome (pSS). The present aim was to investigate the activation status of different STAT proteins in peripheral blood (PB) lymphocytes and monocytes, and their correlations with clinical parameters in patients with pSS. To this end, PB samples were drawn from 16 patients with active pSS and 16 healthy blood donors, and the phosphorylation of STAT-1, -3, -4, -5 and -6 proteins was studied in T cells, B cells and monocytes using multi-colour flow cytometry.

The activity of JAK-STAT pathways in rheumatoid arthritis: constitutive activation of STAT3 correlates with interleukin 6 levels.

Objective: Many cytokines involved in RA activate the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathways. Therapeutic drugs that inhibit these pathways are being developed for RA. To investigate disease-related alterations in the activity of JAK-STAT pathways in RA, we studied the expression and activation of STAT1 and STAT3 in unstimulated and cytokine-stimulated cells and determined the levels of circulating cytokines.

Expression analysis of Tudor-SN protein in mouse tissues.

Tudor-SN (SND1, p100) has been shown to function as a transcriptional coactivator as well as a modulator of RNA metabolism and biogenesis and a component in the RNA-induced silencing complex (RISC). Tudor-SN consists of five repeats of staphylococcus nuclease-like domains (SN1-SN5) and, a Tudor domain implicated in binding to methylated ligands. The protein is highly conserved through evolution from fission yeast to mammals and it exists as a single gene without any close homologs.

Chronic back pain in patients with rheumatoid arthritis and in a control population: prevalence and disability--a 5-year follow-up.

Objectives: To determine the prevalence of chronic back pain and its changes over 5 years in patients with RA compared with community controls and to evaluate the influence of chronic back pain in functional capacity, general pain and global health.

Methods: The prevalence of chronic back pain in 1076 patients with RA and in 1491 community controls was evaluated using a mailed questionnaire, which also queried the functional capacity on the HAQ, and general pain and global health on visual analogue scales.

Results: Chronic back pain was more frequent in the general population than in patients with RA: 19% of patients with RA and 25% of controls reported chronic back pain (P < 0.

Expression of IL-10 family cytokines in rheumatoid arthritis: elevated levels of IL-19 in the joints.

Objectives: Interleukin (IL)-10 functions as an anti-inflammatory cytokine in rheumatoid arthritis (RA). New IL-10 family cytokines IL-19, IL-20, IL-22, IL-24, and IL-26 have recently been discovered. Information concerning the expression and function of these cytokines in autoimmune diseases is currently limited.

Cost-effectiveness of infliximab in the treatment of rheumatoid arthritis in clinical practice.

Objective: We evaluated the cost-effectiveness of infliximab therapy in Finnish RA patients in a real-life clinical setting and identified factors influencing it, using the national register of biological treatment (ROB-FIN).

Methods: A cost-utility analysis was performed, derived from EQ-5D, and related to HAQ score and disease activity using multiple regression. QALYs were calculated based on these utilities, using patient-level data up to the last control registered.

The expression of SOCS is altered in rheumatoid arthritis.

Objectives: Cytokines play a key pathogenic role in rheumatoid arthritis (RA). Several cytokines signal through the JAK-STAT pathway, which is negatively regulated by the suppressors of cytokine signalling (SOCS) proteins. Since SOCS protein levels can profoundly modulate cellular responses to cytokines, we have investigated their expression in chronic RA.

TCRzetadim lymphocytes define populations of circulating effector cells that migrate to inflamed tissues.

The T-cell receptor zeta (TCRzeta) chain is a master sensor and regulator of lymphocyte responses. Loss of TCRzeta expression has been documented in infectious, inflammatory, and malignant diseases, suggesting that it may serve to limit T-cell reactivity and effector responses at sites of tissue damage. These observations prompted us to explore the relationship between TCRzeta expression and effector function in T cells.