Fei Gu

Mesenchymal stem cell transplantation for diffuse alveolar hemorrhage in SLE

Background. A 19-year-old girl was diagnosed with systemic lupus erythematosus, based on findings of arthritis, malar rash, positive antinuclear antibody test and high levels of antibodies to double-stranded DNA. Two months after diagnosis, the patient presented with a sudden drop in blood hemoglobin level. Several days later, she developed bloody sputum, rapidly progressive dyspnea and hypoxemia. High-resolution CT showed diffuse alveolar infiltrates in both lung fields.Investigations. Physical examination, complete blood count, erythrocyte sedimentation rate, urinalysis, 24-h urine protein excretion, fecal occult blood test, d-dimer test, acid hemolysis test, activated partial thromboplastin time and prothrombin time, direct and indirect Coombs tests, bone marrow smear, arterial blood gas, sputum smear and culture, and high-resolution CT scan of the chest.Diagnosis. Diffuse alveolar hemorrhage associated with systemic lupus erythematosus.Management. The patient did not respond to pulsed intravenous methylprednisolone (two courses of 500 mg per day for 3 days) and intravenous immunoglobulin (20 g per day for 5 days). The patient was referred to a specialist treatment center for allogenic transplantation using umbilical-cord-derived mesenchymal stem cells. She underwent transplantation with an infusion of 8 × 107 mesenchymal stem cells. After showing dramatic improvements in her clinical condition, oxygenation level, radiographic and hematological status, the patient was discharged from hospital approximately 5 weeks after undergoing transplantation.

Artesunate inhibits type I interferon-induced production of macrophage migration inhibitory factor in patients with systemic lupus erythematosus

Objective Macrophage migration inhibitory factor (MIF) is a key regulator of both atherosclerosis and systemic lupus erythematosus (SLE), yet factors leading to its overproduction remain unclear. To explore regulation of MIF in SLE, we studied effects and potential mechanisms of type I interferon (IFN) and artesunate (ART), an antimalarial agent extracted from Chinese herbs, on levels of MIF. Methods Serum and peripheral blood cells from SLE patients and healthy controls were measured for MIF levels by ELISA and type I IFN-inducible gene expressions by real-time PCR, respectively, and assessed for associations by Spearman correlation. ART was added to human umbilical vein endothelial cell (HUVEC) cultures with or without prior IFNα-1b stimulation and to SLE peripheral blood mononuclear cell (PBMC) cultures. Protein levels of STATs and phosphorylated (p-) STATs in HUVECs were determined by Western blotting. Results Serum MIF levels were elevated in SLE patients and positively associated with disease activity (r = 0.86, p < 0.0001), accumulated damage (r = 0.34, p < 0.05), and IFN scores in SLE PBMCs (r = 0.74, p = 0.0002). The addition of IFNα-1b promoted MIF production in a time- and dose-dependent manner in HUVEC cultures. ART could inhibit expressions of IFN-inducible genes (LY6E and ISG15) in both HUVEC and SLE PBMC cultures, and suppress MIF production and over-expression of p-STAT1, but not p-STAT3 or STAT5, induced by IFNα-1b stimulation. IFNγ-induced expression of p-STAT1 in HUVECs was not inhibited by ART. Conclusion MIF could be regulated by type I IFN in SLE patients. ART counteracts the effect of IFNα to inhibit MIF production by blocking STAT1 phosphorylation and thus may have therapeutic potential for SLE-associated atherosclerosis.

High remission and low relapse with prolonged intensive DMARD therapy in rheumatoid arthritis (PRINT): A multicenter randomized clinical trial.

Objectives: To determine whether prolonged intensive disease-modifying antirheumatic drug (DMARD) treatment (PRINT) leads to high remission and low relapse rates in patients with severe rheumatoid arthritis (RA). Methods: In this multicenter, randomized and parallel treatment trial, 346 patients with active RA (disease activity score (28 joints) [DAS28] (erythrocyte sedimentation rate [ESR]) > 5.1) were enrolled from 9 centers. In phase 1, patients received intensive treatment with methotrexate, leflunomide, and hydroxychloroquine, up to 36 weeks, until remission (DAS28 ⩽ 2.6) or a low disease activity (2.6 < DAS28 ⩽ 3.2) was achieved. In phase 2, patients achieving remission or low disease activity were followed up with randomization to 1 of 2 step-down protocols: leflunomide plus hydroxychloroquine combination or leflunomide monotherapy. The primary endpoints were good European League Against Rheumatism (EULAR) response (DAS28 (ESR) < 3.2 and a decrease of DAS28 by at least 1.2) during the intensive treatment and the disease state retention rate during step-down maintenance treatment. Predictors of a good EULAR response in the intensive treatment period and disease flare in the maintenance period were sought. Results: A good EULAR response was achieved in 18.7%, 36.9%, and 54.1% of patients at 12, 24, and 36 weeks, respectively. By 36 weeks, 75.4% of patients achieved good and moderate EULAR responses. Compared with those achieving low disease activity and a high health assessment questionnaire (HAQ > 0.5), patients achieving remission (DAS28 ⩽ 2.6) and low HAQ (⩽ 0.5) had a significantly higher retention rate when tapering the DMARDs treatment (P = 0.046 and P = 0.01, respectively). There was no advantage on tapering to combination rather than monotherapy. Conclusions: Remission was achieved in a proportion of patients with RA receiving prolonged intensive DMARD therapy. Low disease activity at the start of disease taper leads to less subsequent flares. Leflunomide is a good maintenance treatment as single treatment.

Efficacy and safety of weekly leflunomide for the treatment of early rheumatoid arthritis: a randomized, multi-center study.

The aim of this study was to determine the efficacy and safety of a weekly dose of leflunomide (50 mg/week) in early rheumatoid arthritis patients with mild or moderate disease activity.

THU0552 Artesunate Modulates Atherosclerosis Related Factors through the Inhibition of Type I Interferon in Patients with Systemic Lupus Erythematosus

Background The chronic inflammatory nature of systemic lupus erythematosus (SLE) is hypothesized to lead to many co-morbidities including premature accelerated atherosclerosis. Objectives In this study, we: 1) assessed levels of several classic atherosclerosis related factors in SLE patients, including macrophage migration inhibitory factor (MIF), vascular endothelial growth factor (VEGF) and numbers of peripheral endothelial progenitor cells (EPCs), 2) explored the mechanisms by which SLE causes premature accelerated atherosclerosis, 3) investigated the potential role of artesunate (ART) in ameliorating SLE-associated atherosclerosis. Methods SLE disease activity was assessed by the Systemic Lupus Erythematosus Disease Activity Index. VEGF and MIF levels in serum and cultured supernatant were determined by ELISA. Peripheral CD34+KDR+ cells were measured by flow cytometry to represent EPCs. Human umbilical vein endothelial cells (HUVECs) and PBMCs were cultured with or without the presence of 1000 U/ml interferon (IFN)α-1b for 24 hours. To detect the effect of ART on these cells, ART at a dose of 5 or 20 μmol/L was added to the culture system for 12 and 24 hours. Results SLE patients had high levels of MIF, low levels of VEGF and reduced numbers of EPCs, which were correlated with disease activity and aberrant IFN-inducible gene expressions. In vitro experiments indicated that MIF levels significantly elevated after IFNα treatment, while VEGF levels varied at different time periods by showing a decline after 12 hours stimulation but an incline at 24 hours. ART significantly suppressed IFN-α promoted VEGF and MIF production at 24 hours. Conclusions ART could modulate atherosclerosis related factors through the inhibition of type I IFN in SLE patients, thus may have therapeutic potential for SLE-associated atherosclerosis. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.3480