Modulation of T Cell Function by Combination of Epitope Specific and Low Dose Anticytokine Therapy Controls Autoimmune Arthritis

Innate and adaptive immunity contribute to the pathogenesis of autoimmune arthritis by generating and maintaining inflammation, which leads to tissue damage. Current biological therapies target innate immunity, eminently by interfering with single pro-inflammatory cytokine pathways. This approach has shown excellent efficacy in a good proportion of patients with Rheumatoid Arthritis (RA), but is limited by cost and side effects. Adaptive immunity, particularly T cells with a regulatory function, plays a fundamental role in controlling inflammation in physiologic conditions. A growing body of evidence suggests that modulation of T cell function is impaired in autoimmunity. Restoration of such function could be of significant therapeutic value. We have recently demonstrated that epitope-specific therapy can restore modulation of T cell function in RA patients. Here, we tested the hypothesis that a combination of anti-cytokine and epitope-specific immunotherapy may facilitate the control of autoimmune inflammation by generating active T cell regulation. This novel combination of mucosal tolerization to a pathogenic T cell epitope and single low dose anti-TNFα was as therapeutically effective as full dose anti-TNFα treatment. Analysis of the underlying immunological mechanisms showed induction of T cell immune deviation

Screening for proximal coronary artery anomalies with 3-dimensional MR coronary angiography

Under 35 years of age, 14% of sudden cardiac death in athletes is caused by a coronary artery anomaly (CAA). Free-breathing 3-dimensional magnetic resonance coronary angiography (3D-MRCA) has the potential to screen for CAA in athletes and non-athletes as an addition to a clinical cardiac MRI protocol. A 360 healthy men and women (207 athletes and 153 non-athletes) aged 18–60 years (mean age 31 ± 11 years, 37% women) underwent standard cardiac MRI with an additional 3D-MRCA within a maximum of 10 min scan time. The 3D-MRCA was screened for CAA. A 335 (93%) subjects had a technically satisfactory 3D-MRCA of which 4 (1%) showed a malignant variant of the right coronary artery (RCA) origin running between the aorta and the pulmonary trunk. Additional findings included three subjects with ventral rotation of the RCA with kinking and possible proximal stenosis, one person with additional stenosis and six persons with proximal myocardial bridging of the left anterior descending coronary artery. Coronary CT-angiography (CTA) was offered to persons with CAA (the CAA was confirmed in three, while one person declined CTA) and stenosis (the ventral rotation of the RCA was confirmed in two but without stenosis, while two people declined CTA). Overall 3D MRCA quality was better in athletes due to lower heart rates resulting in longer end-diastolic resting periods. This also enabled faster scan sequences. A 3D-MRCA can be used as part of the standard cardiac MRI protocol to screen young competitive athletes and non-athletes for anomalous proximal coronary arteries