ObjectiveRegulatory T cells (Tregs) prevent autoimmunity and control inflammation. Consequently, any autoimmune or inflammatory disease reveals a Treg insufficiency. As low-dose interleukin-2 (ld-IL2) expands and activates Tregs, it has a broad therapeutic potential.AimWe aimed to assess this potential and select diseases for further clinical development by cross-investigating the effects of ld-IL2 in a single clinical trial treating patients with 1 of 11 autoimmune diseases.MethodsWe performed a prospective, open-label, phase I–IIa study in 46 patients with a mild to moderate form of either rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, psoriasis, Behcet’s disease, granulomatosis with polyangiitis, Takayasu’s disease, Crohn’s disease, ulcerative colitis, autoimmune hepatitis and sclerosing cholangitis. They all received ld-IL2 (1 million IU/day) for 5 days, followed by fortnightly injections for 6 months. Patients were evaluated by deep immunomonitoring and clinical evaluation.Resultsld-IL2 was well tolerated whatever the disease and the concomitant treatments. Thorough supervised and unsupervised immunomonitoring demonstrated specific Treg expansion and activation in all patients, without effector T cell activation. Indication of potential clinical efficacy was observed.ConclusionThe dose of IL-2 and treatment scheme used selectively activate and expand Tregs and are safe across different diseases and concomitant treatments. This and preliminary indications of clinical efficacy should licence the launch of phase II efficacy trial of ld-IL2 in various autoimmune and inflammatory diseases.Trial registration numberNCT01988506.

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Pulmonary function loss in patients with Duchenne muscular dystrophy (DMD) is progressive and leads to pulmonary insufficiency. The purpose of this study in 10-18 year old patients with DMD is the assessment of the inter-correlation between pulmonary function tests (PFTs), their reliability and the association with the general disease stage measured by the Brooke score. Dynamic PFTs (peak expiratory flow [PEF], forced vital capacity [FVC], forced expiratory volume in one second [FEV1]) and maximum static airway pressures (MIP, MEP) were prospectively collected from 64 DMD patients enrolled in the DELOS trial (ClinicalTrials.gov, number NCT01027884). Baseline PEF percent predicted (PEF%p) was <80% and patients had stopped taking glucocorticoids at least 12 months prior to study start. At baseline PEF%p, FVC%p and FEV1%p correlated well with each other (Spearman's rho: PEF%p-FVC%p: 0.54; PEF%p-FEV1%p: 0.72; FVC%p-FEV1%p: 0.91). MIP%p and MEP%p correlated well with one another (MIP%p-MEP%p: 0.71) but less well with PEF%p (MIP%p-PEF%p: 0.40; MEP%p-PEF%p: 0.41) and slightly better with FVC%p (MIP%p-FVC%p: 0.59; MEP%p-FVC%p: 0.74). The within-subject coefficients of variation (CV) for successive measures were 6.97% for PEF%p, 6.69% for FVC%p and 11.11% for FEV1%p, indicating that these parameters could be more reliably assessed compared to maximum static airway pressures (CV for MIP%p: 18.00%; MEP%p: 15.73%). Yearly rates of PFT decline (placebo group) were larger in dynamic parameters (PEF%p: -8.9% [SD 2.0]; FVC%p: -8.7% [SD 1.1]; FEV1%p: -10.2% [SD 2.0]) than static airway pressures (MIP%p: -4.5 [SD 1.3]; MEP%p: -2.8 [SD 1.1]). A considerable drop in dynamic pulmonary function parameters was associated with loss of upper limb function (transition from Brooke score category 4 to category 5). In conclusion, these findings expand the understanding of the reliability, correlation and evolution of different pulmonary function measures in DMD patients who are in the pulmonary function decline phase.

Although documented in AD, the role of APOE remains unclear in ALS. APOE phenotype and plasma levels were measured in 403 patients with ALS and were correlated with clinical parameters and survival time. No correlations were observed between the APOE phenotype and these variables. In contrast, APOE plasma levels were correlated with both rate of deterioration and survival time and appeared to be an important risk factor for decreased survival time with a relative risk of 0.647 (95% CI: 0.465 to 0.901; p = 0.01).

BackgroundAnkle strength is often impaired in some of the most common neuromuscular disorders. Consequently, strength generated around this joint is important to assess, because it has a great impact on balance and gait. The objectives of this study were to establish normative data and predictive equations for both ankle dorsi- and plantar-flexion strength from a population of healthy subjects (children and adults), to assess the reliability of the measurements and to study the feasibility of using a novel dynamometer on a group of patients with a neuromuscular disorder.MethodsMeasurements of maximal isometric torque for dorsi- and plantar-flexion were performed on 345 healthy subjects from 5 to 80 years of age. The feasibility of the method was tested on nine patients diagnosed with type 2A limb girdle muscular dystrophy.ResultsThe results documented normal strength values depending on gender and age on ankle dorsi- and plantar-flexion. The reliability of the technique was good with no evaluator effect and a small learning effect. The dynamometer was found suitable in the group of patients, even very weak.ConclusionsThe device developed was both reliable and accurate in assessing both ankle dorsi-flexion and plantar-flexion torque measurements from weak patients and children to strong healthy adults. Norms and predictive equations are provided for these two muscle functions.

BackgroundWrist movements become impaired with disease progression in various neuromuscular disorders. With the development of new therapies, thorough measurement of muscle strength is crucial to document natural disease progression and to assess treatment efficacy. We developed a new dynamometer enabling wrist flexion and extension torque measurement with high sensitivity. The aims of the present study were to collect norms for healthy children and adults, to compute predictive equations, to assess the reliability of the measurements and to test the feasibility of using the device in patients with a neuromuscular disease.MethodsThe peak isometric torque of wrist flexion and extension was measured with the MyoWrist dynamometer in 345 healthy subjects aged between 5 and 80 years old and in 9 patients with limb girdle muscle dystrophy type 2 C (LGMD2C) aged between 16 and 38 years old.ResultsPredictive equations are proposed for the wrist flexion and extension strength in children and adults. Intra-rater and inter-rater reliability was good with ICCs higher than 0.9 for both wrist flexion and extension. However, retest values were significantly higher by 4% than test results. The dynamometer was applied with no difficulty to patients with LGMD2C and was sensitive enough to detect strength as weak as 0.82 N.m. From our models, we quantified the mean strength of wrist extension in LGMD2C patients to 39 ± 17% of their predicted values.ConclusionsThe MyoWrist dynamometer provides reliable and sensitive measurement of both wrist flexion and extension torques. However, a training session is recommended before starting a study as a small but significant learning effect was observed. Strength deficit can be quantified from predictive equations that were computed from norms of healthy children and adults.

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