Bi-ventricular interplay in patients with systemic sclerosis-associated pulmonary arterial hypertension: Detection by cardiac magnetic resonance

<p><i>Objectives</i>: Pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc) has a poor prognosis compared to PAH associated with other connective tissue diseases (CTD). The objective of this study was to examine the difference in hemodynamic state between SSc-PAH and other CTD-PAH by performing cardiac magnetic resonance (CMR) imaging.</p> <p><i>Methods</i>: A single center retrospective analysis was conducted comprising 40 consecutive CTD patients who underwent right heart catheterization and CMR at the same period from January 2010 to October 2015.</p> <p><i>Results</i>: Thirty-two patients had pre-capillary pulmonary hypertension. Of these, 15 had SSc and 17 had other CTD. CMR measurements, particularly the ratio of right to left end-diastolic volume (RVEDV/LVEDV), correlated well with mean pulmonary arterial pressure (mPAP). Conversely, RVEDV/LVEDV and mPAP correlated differently in SSc and non-SSc patients. In SSc patients, the ratio of RVEDV/LVEDV to mPAP was significantly higher compared to non-SSc patients. In the follow-up study, 2 SSc patients exhibited increased RVEDV/LVEDV in spite of decreased mPAP following treatment. Kaplan–Meier analysis revealed poor prognosis of patients with increased RVEDV/LVEDV following treatment.</p> <p><i>Conclusions</i>: Our data indicated that altered bi-ventricular interplay detected at CMR may represent SSc-related cardiac involvement and reflect poor prognosis of SSc-PAH.</p

Interferon-inducible Mx1 protein is highly expressed in renal tissues from treatment-naïve lupus nephritis, but not in those under immunosuppressive treatment

<p><b>Objectives:</b> The aim of this study was to clarify the consequences of Mx1, one of the IFN-inducible proteins, in the peripheral blood as well as in renal tissues in patients with systemic lupus erythematosus (SLE).</p> <p><b>Patients and methods:</b> Mx1 protein concentrations in (PBMCs) from 18 SLE patients mostly in their stable disease status, 11 IgA nephropathy (IgAN) patients, 5 ANCA-associated vasculitis (AAV) patients and 16 healthy controls were measured using enzyme-linked immunosorbent assay (ELISA). Mx1 expression in renal specimens from 18 patients with lupus nephritis (LN), 18 with IgAN and 10 with AAV were evaluated using immunohistochemistry.</p> <p><b>Results:</b> Mx1 protein concentrations in lysates of PBMCs were significantly higher in SLE patients compared with those in other three groups. Mx1-positive area in renal tissues was significantly dominant in both glomeruli and renal tubules of LN compared with other renal diseases. Renal Mx1 protein levels were lower in LN after immunosuppressive treatment, compared with those from immunosuppressant-naïve patients.</p> <p><b>Conclusion:</b> Mx1 levels were upregulated in lupus peripheral blood even when their disease activities were stable. On the other hand, Mx1 was highly expressed in kidneys from patients with LN before treatment, which was decreased after immunosuppressive treatment. These results suggest that Mx1 is a potential marker for the diagnosis of SLE in the peripheral blood and also for the activity of lupus nephritis in the kidney.</p

Maintenance treatment using abatacept with dose reduction after achievement of low disease activity in patients with rheumatoid arthritis (MATADOR) – A prospective, multicenter, single arm pilot clinical trial

<p><b>Objectives:</b> To preliminarily evaluate the feasibility of maintenance therapy with reduced dose of intravenous abatacept (ABT) to 250 mg/body/month after achieving remission or low disease activity (LDA).</p> <p><b>Patients and methods:</b> RA patients treated with ABT at 13 sites were enrolled in this prospective interventional pilot study during the period between March 2013 and March 2015. Inclusion criteria were (1) age at 20 years or older, (2) under treatment with monthly intravenous ABT at approved doses, (3) DAS28-CRP lower than 2.7 at least for 6 months, (4) agreed to join this trial with written informed consent and (5) body weight under 125 kg. Enrolled patients were maintained with intravenous monthly ABT at a reduced dose of 250 mg/body (MATADOR protocol). The primary end point was the proportion of the patients continued with MATADOR protocol at week 48. MATADOR protocol was discontinued upon disease flare or other reasons such as patients’ request or severe adverse event (AE). Disease activities and structural changes were also evaluated.</p> <p><b>Results:</b> Fifty-three patients fulfilled the entry criteria and were followed for 1-year. MATADOR protocol was continued for 1-year in 43 (81%) of the evaluated patients. Three patients experienced severe AEs. Mean DAS28-CRP and remission rate were 1.56 and 88% when ABT reduced and 1.80 and 81% at 1-year, respectively. Structural remission was achieved in 34 out of 42 evaluated patients.</p> <p><b>Conclusions:</b> Reduced dose of intravenous ABT was proposed as a feasible choice for maintenance therapy for RA after achievement of remission/LDA, although further randomized trials would be awaited.</p