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Objectives Clinical phenotyping and predicting treatment responses in SLE patients is challenging. Extensive blood transcriptional profiling has identified various gene modules that are promising for stratification of SLE patients. We aimed to translate existing transcriptomic data into simpler gene signatures suitable for daily clinical practice. Methods Real-time PCR of multiple genes from the IFN M1.2, IFN M5.12, neutrophil (NPh) and plasma cell (PLC) modules, followed by a principle component analysis, was used to identify indicator genes per gene signature. Gene signatures were measured in longitudinal samples from two childhood-onset SLE cohorts (n  = 101 and n  = 34, respectively), and associations with clinical features were assessed. Disease activity was measured using Safety of Estrogen in Lupus National Assessment (SELENA)-SLEDAI. Cluster analysis subdivided patients into three mutually exclusive fingerprint-groups termed (1) all-signatures-low, (2) only IFN high (M1.2 and/or M5.12) and (3) high NPh and/or PLC. Results All gene signatures were significantly associated with disease activity in cross-sectionally collected samples. The PLC-signature showed the highest association with disease activity. Interestingly, in longitudinally collected samples, the PLC-signature was associated with disease activity and showed a decrease over time. When patients were divided into fingerprints, the highest disease activity was observed in the high NPh and/or PLC group. The lowest disease activity was observed in the all-signatures-low group. The same distribution was reproduced in samples from an independent SLE cohort. Conclusions The identified gene signatures were associated with disease activity and were indicated to be suitable tools for stratifying SLE patients into groups with similar activated immune pathways that may guide future treatment choices. [ABSTRACT FROM AUTHOR]

Question: Which is the best strategy to achieve (drug-free) inactive disease in juvenile idiopathic arthritis (JIA)?Methods: In a randomised, single-blinded, study in disease-modifying anti-rheumatic drug (DMARD)-naive patients with JIA, three treatment-strategies were compared: (1) sequential DMARD-monotherapy (sulfasalazine or methotrexate (MTX)), (2) combination therapy MTX + 6 weeks prednisolone and (3) combination therapy MTX +etanercept. Treatment-to-target entailed 3-monthly DMARD/biological adjustments in case of persistent disease activity, with drug tapering to nil in case of inactive disease.After 24 months, primary outcomes were time-to-inactive-disease and time-to-flare after DMARD discontinuation. Secondary outcomes were adapted ACRPedi30/50/70/90 scores, functional ability and adverse events.Results: 94 children (67 % girls) aged median (IQR) 9.1 (4.6-12.9) years were enrolled: 32 in arms 1 and 2, 30 in arm 3. At baseline visual analogue scale (VAS) physician was mean 49 (SD 16) mm, VAS patient 53 (22) mm, erythrocyte sedimentation rate 12.8 (14.7), active joints median 8 (5-12), limited joints 2.5 (1-4.8) and Childhood Health Assessment Questionnaire score mean 1.0 (0.6).After 24 months, 71% (arm 1), 70% (arm 2) and 72% (arm 3) of patients had inactive disease and 45% (arm 1), 31% (arm 2) and 41% (arm 3) had drug-free inactive disease. Time-to-inactive-disease was median 9.0 (5.3-15.0) months in arm 1, 9.0 (6.0-12.8) months in arm 2 and 9.0 (6.0-12.0) months in arm 3 (p=0.30). Time-to-flare was not significantly different (overall 3.0 (3.0-6.8) months, p=0.7). Adapted ACR pedi-scores were comparably high between arms. Adverse events were similar.Conclusion: Regardless of initial specific treatments, after 24 months of treatment-to-target aimed at drug-free inactive disease, 71% of recent-onset patients with JIA had inactive disease (median onset 9 months) and 39% were drug free. Tightly controlled treatment-to-target is feasible.Trial Registration Number: 1574. [ABSTRACT FROM AUTHOR]

Background aims. Infusion of mesenchymal stromal cells (MSCs) has been reported to be an effective treatment modality for acute graft-versus-host disease, and MSCs have been considered for use in the treatment of patients with autoimmune diseases. Before contemplating clinical studies with MSCs in patients with systemic juvenile idiopathic arthritis (sJIA), the immunomodulatory capacity of MSCs in this setting needs to be explored. A comparative analysis of bone marrow-derived MSCs from children with sJIA and healthy pediatric controls was performed. Methods. MSCs were successfully expanded from 11 patients with sJIA and 10 controls. The phenotype, differentiation and iinmunomodulatory capacity of these MSCs were compared. The effect of immunosuppressive drugs on MSC function was also investigated. Results. MSCs from patients with sJIA and controls showed no differences in their suppressive effect using control peripheral blood mononuclear cells. Furthermore, the suppression of the response of peripheral blood mononuclear cells from patients with sJIA by autologous sJIA MSCs and allogeneic control MSCs was comparable. The immunosuppressive effect of both groups of MSCs was diminished in the presence of indomethacin (P < 0.05). MSCs from patients with sJIA and controls suppressed interleukin-2-induced natural killer cell activation to a similar extent. In addition, MSCs of patients with sJIA and controls inhibited the differentiation of monocytes to dendritic cells. Conclusions. This is the first explorative study in a significant cohort of patients with sJIA to evaluate the effect of MSCs on adaptive and innate immune responses. The comparable immunosuppressive characteristics of MSCs derived from patients with sJIA to age-matched controls support the potential use of patient-derived MSCs in the treatment of sJIA. [ABSTRACT FROM AUTHOR]

Over the past decades, the intestinal microbiota has increasingly gained attention in studies addressing the pathophysiology of (pediatric) autoimmune diseases, including inflammatory joint diseases, inflammatory bowel disease (IBD), and type 1 diabetes. In this study, we have analyzed the composition of gut microbiota of newly diagnosed juvenile idiopathic arthritis (JIA) patients, prior to initiation of disease-modifying antirheumatic drugs (DMARDs). Fecal microbiota profiles of 8 JIA patients (median age: 11.1 years, 6 girls) were compared with 22 healthy age-matched controls using IS-pro, a 16S-23S interspacer (IS) region-based, eubacterial molecular detection technique. By partial least squares discriminant analysis (PLS-DA), microbiota profiles of JIA and controls could significantly be discriminated based on a limited set of species belonging to the phylum Bacteroidetes (Fig. 2), but not within other phyla, with a sensitivity of 88%, specificity of 73% (Fig. 3), and area under the curve (AUC) 0.87 (95% CI: 0.73-0.87). These discriminative species have been considered to be part of the microbial core in healthy children. Conclusion Our findings add to the increasing notion that the gut microbiota may be involved in the pathophysiology of JIA. Species involved in the discrimination between JIA and controls are members of the microbial core in the healthy state. Expanding knowledge on JIA-specificmicrobial signatures and host interactions may open avenues to explore options to develop individualized, microbiota-based preventive, and therapeutic interventions in JIA. [ABSTRACT FROM AUTHOR]