0000000000117044
AUTHOR
Bernd C. Kieseier
Safety and clinical outcomes of rituximab therapy in patients with different autoimmune diseases: experience from a national registry (GRAID)
Introduction: Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard-of-care. The objective of this study was to evaluate the safety and clinical outcomes of rituximab in several standard-of-care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin's lymphoma in a real-life clinical setting. Methods: Patients who received rituximab having shown an inadequate response to standard-of-care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune…
Dimethyl fumarate alters intracellular Ca2+ handling in immune cells by redox-mediated pleiotropic effects
Dimethyl fumarate (DMF) is widely used to treat the human autoimmune diseases multiple sclerosis (MS) and psoriasis. DMF causes short-term oxidative stress and activates the antioxidant response via the transcription factor Nrf2 but its immunosuppressive effect is not well understood. Immune cell activation depends on calcium signaling which itself is influenced by the cellular redox state. We therefore measured calcium, reactive oxygen species levels and glutathione content in lymphocytes from immunized mice before onset of experimental autoimmune encephalomyelitis, in peripheral blood mononuclear cells from MS patients treated with DMF, and in mouse splenocytes treated ex vivo with DMF. T…
Successful Replication of GWAS Hits for Multiple Sclerosis in 10,000 Germans Using the Exome Array
Genome-wide association studies (GWAS) successfully identified various chromosomal regions to be associated with multiple sclerosis (MS). The primary aim of this study was to replicate reported associations from GWAS using an exome array in a large German study. German MS cases (n = 4,476) and German controls (n = 5,714) were genotyped using the Illumina HumanExome v1-Chip. Genotype calling was performed with the Illumina Genome Studio(TM) Genotyping Module, followed by zCall. Single-nucleotide polymorphisms (SNPs) in seven regions outside the human leukocyte antigen (HLA) region showed genome-wide significant associations with MS (P values < 5 × 10(-8) ). These associations have been repor…
Immunelectronmicroscopic characterization of T4 and T8 lymphocytes and natural killer cells in neuronal ceroid-lipofuscinosis.
CD4+, CD8+, and CD56+ cells were isolated with the immunomagnetic separation technique from peripheral blood mononuclear cells (PBMC) of 3 patients with neuronal ceroid-lipofuscinosis : one patient each with infantile (INCL), late infantile (LINCL), and juvenile (JNCL) neuronal ceroid-lipofuscinoses, all studied by light (LM) and electron (EM) microscopy. To compare the pathology of these cells with affected cells in other types of lysosomal diseases, the separation was also performed with PBMC of 1 patient with mucolipidosis (ML) type II, 2 patients with mucopolysaccharidosis (MPS) type I, and 4 patients with MPS type III. Disease-specific lysosomal inclusions were identified in CD4+, CD8+…
The metalloproteinase-disintegrin ADAM10 is exclusively expressed by type I muscle fibers.
ADAM10 (Kuzbanian) is a member of a recently discovered family of membrane-anchored metalloproteinases with a complex and conserved domain structure. In part, these metalloproteinases have been implicated in muscle formation. Herein the expression pattern of ADAM10 in human skeletal muscle was studied. ADAM10 was found to be present in human myoblasts and to be exclusively expressed in type I fibers, suggesting that it may be critical in muscle fiber differentiation.
The cell-specific expression of metalloproteinase-disintegrins (ADAMs) in inflammatory myopathies
Inflammatory cell invasion and cytokine activation are important steps in the pathogenesis of immune-mediated diseases of muscle. Metalloproteinase-disintegrins (ADAMs) are considered to play a critical role in leukocyte migration by promoting cellular adhesion, cleavage of molecules of the extracellular matrix and shedding of membrane bound cytokines. Here, we report the expression patterns of ADAM8, ADAM9, ADAM10, ADAM12, ADAM17 and ADAM19 in cultured human myoblasts and peripheral blood mononuclear cells (PBMCs) in vitro, as well as in biopsies from patients suffering from polymyositis (PM), dermatomyositis (DM), inclusion body myositis (IBM) and non-inflammatory controls. We observed an…