BackgroundThe value of joint ultrasonography (US) in the prediction of clinical arthritis in individuals at risk of developing rheumatoid arthritis (RA) is still a point of debate, due to varying scanning protocols and different populations. We investigated whether US abnormalities assessed with a standard joint protocol can predict development of arthritis in seropositive patients with arthralgia.MethodsAnti-citrullinated protein antibodies and/or rheumatoid factor positive patients with arthralgia, but without clinical arthritis were included. US was performed at baseline in 16 joints: bilateral metacarpophalangeal 2–3, proximal interphalangeal 2–3, wrist and metatarsophalangeal (MTP) joints 2–3 and 5. Images were scored semi-quantitatively for synovial thickening and for positive signs on power Doppler (PD). Association between US abnormalities and arthritis development at the joint and at the patient level was evaluated. Also, we investigated the added value of US over clinical parameters.ResultsOut of 163 patients who underwent US examination, 51 (31%) developed clinical arthritis after a median follow-up time of 12 (interquartile range 5–24) months, of which 44 (86%) satisfied the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for RA. US revealed synovial thickening and PD in at least one joint in 49 patients (30%) and 7 patients (4%), respectively. Synovial thickening was associated with both development and timing of clinical arthritis in any joint (patient level) when MTP joints were excluded from the US assessment (odds ratio 6.6, confidence interval (CI) 1.9–22), and hazard ratio 3.4, CI 1.6–6.8, respectively, with a mean time to arthritis of 23 versus 45 months when synovial thickening was present versus not present). There was no association between US and arthritis development at the joint level. Predictive capacity was highest in the groups with an intermediate and high risk of developing arthritis based on a prediction rule with clinical parameters.ConclusionsSynovial thickening on US predicted clinical arthritis development at the patient level in seropositive patients with arthralgia when MTPs were excluded from the US assessment. Positive PD signs were infrequently seen in these at-risk individuals and was not predictive. In patients at intermediate risk of RA, US may help to identify those at higher risk of developing arthritis.Electronic supplementary materialThe online version of this article (10.1186/s13075-018-1767-9) contains supplementary material, which is available to authorized users.

Background14-3-3η (eta) is a novel serum/plasma protein biomarker involved in the upregulation of inflammatory and joint damage factors. We analysed the association of 14-3-3η with the development of clinically apparent arthritis in a cohort of subjects with arthralgia and positivity for at least one serologic marker: rheumatoid factor (RF) or anti-citrullinated protein antibody (ACPA).MethodsMeasurement of 14-3-3η in plasma collected on entry into the cohort. For this study, 144 subjects with a minimum of 2.5 (median and maximum 5) years of follow-up were available. The relationship between presence and levels of 14-3-3η and development of arthritis was investigated.ResultsArthritis occurred in 43 (30 %) of the 144 subjects after a median of 15 months. 14-3-3η was detectable up to 5 years before onset of clinical arthritis and was present significantly more often (36 % versus 14 %; relative risk 2.5, 95 % confidence interval 1.2–5.6; p = 0.02) and at significantly higher levels (median 0.95 versus 0.28 ng/ml; p = 0.02) in subjects developing arthritis compared with those who did not. 14-3-3η levels/positivity and ACPA, but not RF, were univariately associated with the development of arthritis while generalized linear model analysis with RF and ACPA as obligatory factors could not return an incremental benefit with 14-3-3η.Conclusions14-3-3η was detectable prior to the onset of arthritis and was associated with arthritis development in arthralgia subjects pre-selected for positivity of RF or ACPA. Its power to predict onset of arthritis independent of ACPA and RF requires a new study in which patients are not pre-selected based on ACPA and/or RF seropositivity.

BackgroundMultiple lymphocyte subsets like T and B cells have been connected to joint infiltration and inflammation in rheumatoid arthritis (RA). Identification of leucocyte subsets that are dysregulated in arthritis development could provide insight into the aetiology of RA. This study aimed to investigate the composition of the peripheral blood components, i.e. CD14+ monocytes, CD4+ and CD8+ T lymphocytes (CD3+), CD80+, C-X-C chemokine receptor 3 (CXCR3)+ and CD27+ B lymphocytes (CD19+), CD16+CD56+CD3− natural killer (NK) cells and activated CD56+CD3+ T cells, for association with arthritis development in patients with arthralgia.MethodsPeripheral blood was collected from 89 patients with early RA (disease duration <6 months), 37 healthy controls (HC) and 113 patients with arthralgia (22 developed arthritis within ≤1 year, 18 developed arthritis after >1 year and 73 did not develop arthritis). Absolute numbers of monocytes and lymphocyte subsets in whole heparinized blood were determined with flow cytometry using quantification beads in combination with fluorescent labelled antibodies for T cells, B cells, monocytes, NK cells and activated T cells.ResultsIn patients with early RA, significant decreases in numbers of (activated) T cells, CD80+ and memory B cells and a trend towards smaller numbers of CD8+ T cells was observed compared to HC. Similar differences were seen in patients with arthralgia who developed or did not develop arthritis (non-converters), with significantly decreased CD8+ T cells and memory B cells. Patients with arthralgia who developed arthritis were split into groups that developed arthritis within 1 year (early converters) or after 1 year (late converters). Late converters had a significantly decreased number of CD8+ T cells compared to non-converters; early converters had a decreased number of memory B cells. Longitudinal analysis of converters showed a significant relative increase in CD80+ B cells towards the conversion time point compared to 24 months prior to conversion.ConclusionsThis study revealed that patients with arthralgia who develop arthritis demonstrate a change in cellular immune parameters apparent in the periphery, starting with a decrease in cytotoxic T cells 24 months prior to arthritis development, followed by a decrease in the number of memory B cells 12 months prior to disease onset.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1102-2) contains supplementary material, which is available to authorized users.

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ObjectivesTo describe the development and assess the psychometric properties of the novel ‘Symptoms in Persons At Risk of Rheumatoid Arthritis’ (SPARRA) questionnaire in individuals at risk of rheumatoid arthritis (RA) and to quantify their symptoms.MethodsThe questionnaire items were derived from a qualitative study in patients with seropositive arthralgia. The questionnaire was administered to 219 individuals at risk of RA on the basis of symptoms or autoantibody positivity: 74% rheumatoid factor and/or anticitrullinated protein antibodies positive, 26% seronegative. Validity, reliability and responsiveness were assessed. Eighteen first degree relatives (FDR) of patients with RA were used for comparison.ResultsFace and content validity were high. The test-retest showed good agreement and reliability (1 week and 6 months). Overall, construct validity was low to moderate, with higher values for concurrent validity, suggesting that some questions reflect symptom content not captured with regular Visual Analogue Scale pain/well-being. Responsiveness was low (small subgroup). Finally, the burden of symptoms in both seronegative and seropositive at risk individuals was high, with pain, stiffness and fatigue being the most common ones with a major impact on daily functioning. The FDR cohort (mostly healthy individuals) showed a lower burden of symptoms; however, the distribution of symptoms was similar.ConclusionsThe SPARRA questionnaire has good psychometric properties and can add information to currently available clinical measures in individuals at risk of RA. The studied group had a high burden and impact of symptoms. Future studies should evaluate whether SPARRA data can improve the prediction of RA in at risk individuals.