The thymus in autoimmune Myasthenia Gravis: Paradigm for a tertiary lymphoid organ

In autoimmune Myasthenia Gravis (MG), a neuromuscular disease generally mediated by autoantibodies against the acetylcholine receptor (AChR), the muscle is the target organ of the autoimmune attack, while the thymus seems to be the primary production site of the autoantibodies. In the majority of patients with anti-AChR antibodies, it is characterized by the presence of germinal centers, which contain B cells that produce anti-AChR antibodies. In this review, we summarize recent results regarding neoangiogenic processes, cell infiltration and modified chemokine expression in the MG thymus, which are typical features of secondary lymphoid organs. The structural and functional changes in the MG thymus therefore allow us to declare it to be an archetype for tertiary lymphoid neogenesis providing optimal settings for the interaction between lymphocytes and antigen presenting cells in order to elicit an immune response. We further discuss factors that may have a key role in the transformation of the MG thymus into a tertiary lymphoid organ, such as IFN type I and dsRNA signaling. These factors could also be of importance in other autoimmune diseases, especially those characterized by tertiary lymphoid neogenesis.     

Reduced myocardial perfusion reserve and transmural perfusion gradient in heart transplant arteriopathy assessed by magnetic resonance imaging

OBJECTIVES: The goal of this study was to detect transplant arteriopathy (Tx-CHD) by a reduced myocardial perfusion reserve (MPR) and resting endomyocardial/epimyocardial perfusion ratio (Endo/Epi ratio). BACKGROUND: Transplant arteriopathy often lacks clinical symptoms and is the reason for frequent surveillance angiography in heart transplant (Tx) recipients. Magnetic resonance perfusion imaging (MRPI) allows noninvasive assessment of transmural and selective endomyocardial and epimyocardial perfusion. METHODS: Fifteen healthy volunteers (controls) and three groups (A, B, C) of Tx recipients were included. In controls and patients, MPR (hyperemic/resting perfusion) and Endo/Epi ratio were determined with MRPI after injection of gadolinium-diethylenetriamine pentaacetic acid at rest and during hyperemia (intravenous adenosine). Group A (n = 10) had no left ventricular (LV) hypertrophy and/or prior rejection, while patients in group B (n = 10) had at least one of these characteristics. Patients in group A and B had a normal coronary angiogram and a coronary flow reserve (CFR) of > or =2.5 (CFR = hyperemic/resting blood flow). Group C (n = 7) had Tx-CHD diagnosed by angiography and a reduced CFR (<2.5). RESULTS: In group C, MPR (1.7 +/- 0.5) and Endo/Epi ratio (1.1 +/- 0.2) were significantly reduced compared with controls (4.2 +/- 0.7 and 1.6 +/- 0.3; both p < 0.0001), group A (3.6 +/- 0.7 and 1.6 +/- 0.2; both p < 0.0001) and B (2.7 +/- 0.9, p < 0.01 and 1.4 +/- 0.1, p < 0.04). Transplant arteriopathy can be excluded by an MPR of >2.3 with sensitivity and specificity of 100% and 85%. If LV hypertrophy and prior rejection are excluded, Tx-CHD can be excluded by an Endo/Epi ratio of >1.3 with 100% and 80%. CONCLUSIONS: Magnetic resonance perfusion imaging detects Tx-CHD by a decreased MPR. After exclusion of LV hypertrophy and prior rejection, resting Endo/Epi ratio alone might be sufficient to indicate Tx-CHD.