L. Watson

Background B cells drive antibody formation and T cell activation. This study aimed to describe the clinical indications, efficacy and adverse events (AEs) for the B-cell depleting agent, rituximab, in a large cohort of children with lupus. Methods Prescribing records and the UK JSLE Cohort Study database identified rituximab use. Results Sixty-three patients received 104 courses of intravenous rituximab over a 10-year period. Patients were aged 12.2 (IQR 9.0–13.9) years at diagnosis and 50 (79%) were female. They had disease for 1.4 (0.2–3.0) years at the time of rituximab. Lupus nephritis was the most common indication (36% of first courses). Clinical biomarkers, 2.5 (1.6–4.3) months after treatment, demonstrated a statistically significant improvement in ESR, C3, C4, creatinine, albumin, haemoglobin, anti-dsDNA titres and urine albumin:creatinine ratio. IgG, IgA and IgM levels decreased (p < 0.01). Oral corticosteroid dose significantly reduced after rituximab (dose before 0.26 (0.09–0.44) mg/kg, after 0.17 (0.09–0.30) mg/kg; p = 0.01)). AEs occurred in 19 (18%) of all courses including; delayed second dose (8%), Ig replacement (2%) and infusion reactions (6%; anaphylaxis 2%). The global BILAG score showed a trend toward improvement (before 4.5 (2.0–9.0), after 3.0 (2.0–5.0); p = 0.16). Conclusion Rituximab improves disease activity in children with lupus and serious AEs are infrequent. Controlled studies are required.

Takayasu Arteritis (TA) is a rare, debilitating large vessel vasculitis occurring in patients of all ages, including infants, but the disease most commonly presents in the third decade. Diagnosis is often delayed and consequently TA is associated with significant morbidity and mortality. Accurate methods of monitoring disease activity or damage are lacking and currently rely on a combination of clinical features, blood inflammatory markers, and imaging modalities. In this report we describe a case of a 14-year-old boy with childhood-onset TA who, despite extensive negative investigations, did indeed have on-going active large vessel vasculitis with fatal outcome. Postmortem analysis demonstrated more extensive and active disease than originally identified. This report illustrates and discusses the limitations of current modalities for the detection and monitoring of disease activity and damage in large vessel vasculitis. Clinicians must be aware of these limitations and challenges if we are to strive for better outcomes in TA.

Purpose Sphingosine-1-phosphate (S1P) is an active sphingolipid with chemotactic abilities and has been linked to inflammatory mediators and autoimmune disease. The aim of this study was to assess whether children with juvenile-onset systemic lupus erythematosus (JSLE) express increased systemic and/or urinary concentrations of S1P. Methods A subgroup of patients participating in the UK JSLE Cohort Study, were invited to participate. Cross sectional serum and urine samples were prospectively collected along with demographic and standard clinical data. Results were compared to a cohort of disease controls (Henoch Schonlein Purpura; HSP) and healthy controls (HC). Results The median age of JSLE patients (n = 15) was 13.6 years (7.2–16.9 years). The serum concentrations of S1P in JSLE patients (7.4 uM, IQR 6.3–12.3 uM) were statistically significantly increased when compared to patients with HSP (n = 10; 5.2 uM, IQR 4.0–7.9 uM; p = 0.016) and HCs (n = 10; 3.8 uM, IQR 2.1–5.8 uM; p = 0.003). There was a trend towards increased serum S1P concentrations between patients with active lupus nephritis (n = 8; 8.7 uM, IQR 6.2–15.3 uM) compared to lupus non-nephritis (n = 7; 6.6 uM, IQR 6.3–10.6 uM; p = 0.355). No relationship was found between disease activity markers and S1P. Urine S1P concentrations were no different between JSLE patients (56.0 nM, IQR 40.3–96.6 nM) and HCs (58.7 nM, IQR 0–241.9 nM; p = 0.889). Conclusions We have demonstrated, for the first time, an increased serum concentration of S1P in a cohort of JSLE patients. These findings highlight a role of S1P in the pathophysiology of JSLE that warrants further investigation.