[Lupus and thrombophilia : Antiphospholipid syndrome]. / Lupus und Thrombophilie : Antiphospholipidsyndrom.

Even early on thromboembolic events were observed in patients with systemic lupus erythematosus (SLE) until the antiphospholipid syndrome (APS) was described in the 1980s as an independent disorder. The APS is a systemic autoimmune disease often overlapping with SLE in which antiphospholipid autoantibodies, including lupus anticoagulant, can cause a hypercoagulation state, which clinically by definition is manifested as arterial and venous occlusions or pregnancy complications. The pathophysiology has not yet been entirely delineated and the clinical spectrum of associated concomitant manifestations is large. As the mortality is increased with SLE and simultaneous APS, focused diagnostics and risk assessment are indispensable. According to the recently published recommendations of the European League Against Rheumatism the therapeutic strategy comprises individualized secondary prevention of thromboembolic complications by means of anticoagulation (with unaltered importance of vitamin K antagonists) and thrombocyte aggregation inhibition, usually lifelong. Statins and antimalarial drugs are recommended for vascular protection while immunosuppressive treatment has not so far been sufficiently proven for APS but remains the subject of current research.

Lysosome-Related Effector Vesicles in T Lymphocytes and NK Cells.

Lysosome-related secretory organelles combine metabolic functions of conventional lysosomes with an inducible secretory potential. Specialized variants of such bi-functional organelles are present in several haematopoietic cell types that store, mobilize and/or secrete effector proteins, for example in mast cells, macrophages or cytotoxic effector cells. In the case of T lymphocytes and NK cells, it was believed that secretory lysosomes serve as a common storage and transport compartment for the most relevant cytotoxic effector proteins including FasL, perforin, granzymes and granulysin. However, recent observations suggest that cytotoxic effector cells might be able to mobilize two distinct lysosomal entities in order to react to differential stimulation with either FasL surface appearance or degranulation-associated release of perforin and granzymes. This assumption is supported by the proteomic characterization of enriched organelles from T and NK cells. FasL-associated light lysosomes biochemically segregate from morphologically distinct heavy lysosomes that preferentially contain granzymes, perforin and mature granulysin. Here, we briefly summarize the current knowledge about cargo proteins that are stored and transported in secretory vesicles and how these vesicles might be generated and mobilized. In addition, we describe common features and major differences of the two distinct effector organelles and discuss how these observations might expand existing models of cytotoxic effector function.

Generation of soluble NKG2D ligands: proteolytic cleavage, exosome secretion and functional implications.

The activating natural killer group 2 member D (NKG2D) receptor is expressed on NK cells, cytotoxic T cells and additional T cell subsets. Ligands for human NKG2D comprise two groups of MHC class I-related molecules, the MHC class I chain-related proteins A and B (MICA/B) and 6 UL16-binding proteins (ULBP1-6). While NKG2D ligands are absent from most normal cells, expression is induced upon stress and malignant transformation. In fact, most solid tumours and leukaemia/lymphomas constitutively express at least one NKG2D ligand and thereby are susceptible to NKG2D-dependent immunosurveillance. However, soluble NKG2D ligands are released from tumour cells and can down-modulate NKG2D activation as a means of tumour immune escape. In some tumour entities, levels of soluble NKG2D ligands in the serum correlate with tumour progression. NKG2D ligands can be proteolytically shed from the cell surface or liberated from the membrane by phospholipase C in the case of glycosylphosphatidylinositol (GPI)-anchored molecules. Moreover, NKG2D ligands can be secreted in exosomal microvesicles together with other tumour-derived molecules. Depending on the specific tumour/immune cell setting, these various forms of soluble and/or exosome-bound NKG2D ligands can exert multiple effects on NKG2D/NKG2D ligand interactions. In this review, we focus on the role of various proteases in the shedding of human NKG2D ligands from tumour cells and discuss the not completely unanimous reported functional implications of soluble and exosome-secreted NKG2D ligands for immunosurveillance.

Whole-body MRI and MRA for evaluation of the prevalence of atherosclerosis in a cohort of subjectively healthy individuals.

OBJECTIVES: To assess the prevalence of cardiovascular findings in asymptomatic individuals by means of 1.5-T whole-body magnetic resonance imaging and angiography. METHODS: A cohort of 138 individuals (118 men, 20 women) with a mean age of 54 years (SD ± 7.55) was referred to whole-body MRI at 1.5-T, including contrast-enhanced whole-body MR angiography (MRA) and cardiac MRI. A total of 2,065/2,070 vessel segments (99.8%) and cardiac function were evaluated. RESULTS: Approximately one-fourth of the participating individuals had vascular abnormalities. In 17 subjects (12.3% of all subjects) significant luminal narrowing was observed in at least one vascular segment. Luminal narrowing (mild to severe) was observed in 1 (0.7% of all subjects respectively) of the renal arteries, 7 (5.0%) of the carotid arteries, and 3 (2.2%) of the pelvic and upper leg arteries, and in 17 segments (12.3%) of arteries in the lower leg. In cardiac function and perfusion imaging, wall motion disorders were observed in six patients (4.3%), with additional delayed enhancement and isolated delayed enhancement present in two cases. Functional parameters differed from reference values in 55 cases. CONCLUSIONS: Even in an asymptomatic cohort of middle-aged predominantly male individuals, atherosclerotic disease is not uncommon and is detectable by whole-body MRI. MAIN MESSAGES: • In middle-aged predominantly male individuals, atherosclerotic disease is not uncommon. • Even in an asymptomatic collective, approximately one fourth had vascular abnormalities. • Using whole-body MR angiography (MRA), 99.8% of 2,070 vessel segments could be evaluated.