ACPA conferred the highest risk for arthritis development and had an additive value to RF. However, >30% of ACPA-positive/RF-positive CSA patients did not develop arthritis during the 2-year follow-up. Thus, CSA and information on autoantibodies is insufficient for accurately identifying imminent autoantibody-positive RA.

Autoreactive B cells mediate autoimmune pathology, but exactly how remains unknown. A hallmark of rheumatoid arthritis (RA), a common autoimmune disease, is the presence of disease-specific anticitrullinated protein antibodies (ACPAs). Here, we showed that ACPA-positive B cells in patients with RA strongly expressed T cell–stimulating ligands, produced abundant proinflammatory cytokines, and were proliferative while escaping inhibitory signals. This activated state was found at different degrees in different stages of disease: highest in patients with recent-onset RA, moderate in patients with established RA, and far less pronounced in ACPA-positive individuals “at risk” for developing disease. The activated autoreactive B cell response persisted in patients who achieved clinical remission with conventional treatment. ACPA-positive B cells in blood and synovial fluid secreted increased amounts of the chemoattractant interleukin-8, which attracted neutrophils, the most abundant immune cell in arthritic joints. Tetanus toxoid–specific B cells from the same patients exhibited properties of memory B cells without the activation and proliferation phenotype, but these cells transiently acquired a similar proliferative phenotype upon booster vaccination. Together, these data indicated that continuous antigenic triggering of autoreactive B cells occurs in human autoimmune disease and support the emerging concept of immunological activity that persists under treatment even in clinical remission, which may revise our current concept of treatment targets for future therapeutic interventions. In addition, our data pointed to a pathogenic role of ACPA-positive B cells in the inflammatory disease process underlying RA and favor approaches that aim at their antigen-specific inactivation or depletion.

This study is the first showing that ACPA-positive and ACPA-negative patients have clinical differences in the symptomatic phase preceding clinical arthritis. This contributes to the notion that ACPA-positive and ACPA-negative RA develop differently.

The use of a reference population resulted in a substantial reduction of false-positive results, without influencing the sensitivity. Although common for other tests in medicine, this phenomenon is novel for MRI in the early detection of RA.

The EULAR definition of arthralgia suspicious for progression to RA is sensitive when used to support the rheumatologist's opinion on imminent RA. This validation study shows that the definition, when used as designed, further homogenizes patients that rheumatologists consider at risk for RA. To arrive at a high specificity, the clinical definition needs to be combined with biomarkers.

Objective Ultrasound (US) and magnetic resonance imaging (MRI) are recommended in the diagnostic process of rheumatoid arthritis. Research on its comparability in early disease phases is scarce. Therefore, we compared synovitis and tenosynovitis detected by US and MRI on joint/tendon level. Methods Eight hundred forty joints and 700 tendons of 70 consecutive patients, presenting with inflammatory arthritis or clinically suspect arthralgia, underwent US and MRI of MCP (2–5), wrist and MTP (1–5) joints at the same day. Greyscale (GS) and power Doppler (PD) synovitis were scored according to the modified Szkudlarek method (combining synovial effusion and hypertrophy) and the recently published EULAR-OMERACT method (synovial hypertrophy regardless of the presence of effusion) on static images. US-detected tenosynovitis was scored according to the OMERACT. MRI scans were scored according to the RAMRIS. Test characteristics were calculated on joint/tendon level with MRI as reference. Cut-off for US scores were ≥ 1 and ≥ 2 and for MRI ≥ 1. Results Compared to MRI, GS synovitis according to EULAR-OMERACT (cut-off ≥ 1) had a sensitivity ranging from 29 to 75% for the different joint locations; specificity ranged from 80 to 98%. For the modified Szkudlarek method, the sensitivity was 68–91% and specificity 52–71%. PD synovitis had a sensitivity of 30–54% and specificity 97–99% compared to MRI. The sensitivity to detect GS tenosynovitis was 50–78% and the specificity 80–94%. For PD tenosynovitis, the sensitivity was 19–58% and specificity 98–100%. Conclusion Current data showed that US is less sensitive than MRI in the early detection of synovitis and tenosynovitis, but resulted in only few non-specific findings. The higher sensitivity of MRI is at the expense of less accessibility and higher costs. Electronic supplementary material The online version of this article (10.1186/s13075-019-1824-z) contains supplementary material, which is available to authorized users.

BackgroundIt is suggested that the body posture during urination can influence urodynamic parameters in patients with Lower Urinary Tract Symptoms (LUTS) to an extent approaching pharmacological interventions. In this article, the influence of body position during micturition on maximum urinary flow rate (Qmax), voiding time (TQ) and post-void residual volume (PVR) in healthy males and patients with LUTS is analyzed by means of a systematic review and meta-analysis.Evidence AcquisitionA systematic search was conducted in 14 medical databases. Studies comparing urodynamic parameters in standing versus sitting position were eligible for inclusion. Studies were stratified according to health status of included male participants: healthy individuals and patients with LUTS. Standardized mean differences for Qmax, TQ and PVR were pooled in a random effects model.ResultsEleven articles were included. In men with LUTS, a significantly lower PVR (−24.96 ml; 95%CI −48.70 to −1.23) was shown in sitting position compared to standing. In accordance, Qmax was increased (1.23 ml/s; 95%CI −1.02 to 3.48), and TQ was decreased (−0.62 s; 95%CI −1.66 to 0.42) in sitting position, although these differences did not reach statistical significance. In healthy men, Qmax (0.18 ml/s; 95% CI −1.67 to 2.02), TQ (0.49 s; 95%CI −3.30 to 4.27) and PVR (0.43 ml; 95%CI −0.79 to 1,65) were similar in sitting and standing position.ConclusionFor healthy men, no difference is found in any of the urodynamic parameters. In patients with LUTS, the sitting position is linked with an improved urodynamic profile.

IntroductionA phase of arthralgia may precede the emergence of rheumatoid arthritis (RA). Although several studies have focused on biomarkers, the relevance of this phase for patients is less studied. It is unknown if patients already have functional limitations and if this is correlated to the extent of subclinical inflammation. Therefore, we assessed functional disability in patients with clinically suspect arthralgia (CSA), its association with MRI-detected subclinical inflammation and its course during progression to clinical arthritis.MethodsFrom April 2012 to March 2015, 241 patients had arthralgia for <1 year and were, based on clinical presentation, considered at risk for RA by their rheumatologists. At baseline, Health Assessment Questionnaire (HAQ) scores were determined and unilateral 1.5 T MRI of metacarpophalangeal, wrist and metatarsophalangeal joints were made. Presence of MRI-detected subclinical inflammation was assessed by summing synovitis, tenosynovitis and bone marrow oedema scores (range 0–189). Patients were followed on arthritis development and HAQ scores were repeated when clinical arthritis had developed.ResultsThe median HAQ score at presentation with CSA was 0.50. Higher MRI-inflammation scores were associated with higher HAQ scores (β=0.017, 95% CI=0.004 to 0.030). During median 103 weeks follow-up, 44 patients progressed to clinical arthritis. HAQ scores ≥1.0 were associated with arthritis development (HR=2.50, 95% CI=1.03 to 6.10). Within converters, median HAQ scores did not increase from presentation with CSA to arthritis development (0.88 and 0.75, p=0.36).ConclusionsHAQ scores ≥1.0 at presentation were associated with the development of clinical arthritis. Functional limitations in the prearthritis phase of CSA were as serious as in the early clinical phase, demonstrating the relevance of CSA from patients’ perspectives.