Observational study of patients with relapsing polychondritis (RPC) and brief evaluation of widely used diagnostic criteria. A retrospective analysis of 18 patients with RPC treated in the past 15 years at the Charté-Universitätsmedizin Berlin was performed. Three different diagnostic criteria were applied to our cohort. Sensitivities of diagnostic criteria of McAdam et al., Damiani and Levine and Michet et al. were calculated as well as the 5- and 10-year survival. Analysis of diagnostic criteria revealed a sensitivity of 88.9% using Damiani and Levine criteria, 66.7% for Michet et al. and 50% for McAdam et al., respectively. Modifying the criteria of Michet et al. increases the sensitivity to 88.9%. The 5- and 10-year survival were 100 and 90.9%, respectively. Current diagnostic criteria in RPC should be reappraised covering the diversity of clinical findings with the aim to improve clinical care and research in RPC.
Frontiers in Immunology | www.frontiersin.org March 2020 | Volume 11 | Article 256 Bertolo et al.
Urinary Leukocytes in Lupus Nephritisto identify a signature of activated T cells and macrophages, which appear to reflect leukocytic infiltrates in the kidney. This explorative study has not only confirmed but also extended the knowledge about urinary cells as a future non-invasive biomarker platform for diagnosis and precision medicine in inflammatory renal diseases.
Background/purposeInterleukin-2 (IL-2) is crucial for the growth and survival of regulatory T cells (Treg), and thus for the control of autoimmunity. In previous studies we revealed the significance of an acquired IL-2 deficiency and related Treg defects in the pathogenesis of systemic lupus erythematosus (SLE) .1,2 Accordingly, we showed that low dose IL-2 therapy is capable to correct Treg defects in SLE patients.2,3
Here, we conducted a combined phase I/IIa single centre clinical trial addressing the safety, tolerability, immunological responses and clinical efficacy of a subcutaneous low-dose IL-2 therapy in patients with refractory and active SLE.Methods10 patients with active and refractory SLE (SLEDAI ≥6) were enrolled into the trial and 2 patients were treated “off-label” in advance with the same regimen. The therapeutic regimen consisted of four treatment cycles each with daily subcutaneous injections of recombinant human IL-2 (aldesleukin) at single doses of 0.75, 1.5 or 3.0 million IU on five consecutive days. Cells from peripheral blood were analysed by flow cytometry at every study visit before and one day after each treatment cycle.The primary objective was to show an increase in the percentage of CD25hi cells among CD3+CD4+Foxp3+CD127lo Treg cells by at least 100% (2 fold) after the 4th treatment cycle compared to baseline. Safety and tolerability were evaluated descriptively. Secondary objectives included the clinical responses assessed by SLEDAI and changes in serological and other immunological parameters.ResultsAll 12 patients showed an effective and cycle-dependent increase in the percentage of CD25hi cells among Treg (p<0.001). 10 patients showed a reduction in SLEDAI (83.3%, p<0.05) and 8 patients achieved a clinical response (66.7%) with a complete disappearance of clinical manifestations such as rash, arthritis, myositis and alopecia. Levels of complement were significantly increased after the treatment compared to baseline (p<0.05). No reduction in levels of anti-dsDNA-Abs was observed. Treatment-related adverse events were generally mild and transient.ConclusionLow-dose IL-2 therapy is capable to safely and selectively expand the Treg population and to decrease disease activity in patients with active and refractory SLE. This study provides the basis for larger and placebo-controlled clinical trials.References1. Humrich, et al. Homeostatic imbalance of regulatory and effector T cells due to IL-2 deprivation amplifies murine lupus. Proc Natl Acad Sci USA. 2010;107(1):204–209.2. von Spee-Mayer, et al. Low-dose interleukin-2 selectively corrects regulatory T cell defects in patients with systemic lupus erythematosus. Ann Rheum Dis. 2016;75(7):1407–15.3. Humrich, et al. Rapid induction of clinical remission by low-dose interleukin-2 in a patient with refractory SLE. Ann Rheum Dis. 2015;74(4):791–2.
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