26,017 research outputs found
A “groovy” diagnosis: Eosinophilic fasciitis
No full textAbstract Clinical examination can be the key to pursuing a diagnosis, even in rare diseases. The “groove sign” is a typical finding in eosinophilic fasciitis and can be elicited by elevation of the arm to allow for venous return with visible “grooving” of the veins due to skin thickening
A Transcriptome Array-Based Approach to Link SGLT-2 and Intrarenal Complement C5 Synthesis in Diabetic Nephropathy
No full textDiabetic nephropathy is a common microvascular complication of diabetes mellitus. It is characterized by progressive chronic kidney disease (CKD) with decline of kidney function by hyperfiltration. On a mechanistic level, activation of the complement system has been implicated in the pathogenesis of diabetic nephropathy. Therefore, here we pursued a transcriptome array-based approach to link intrarenal SGLT-2 and the synthesis of distinct complement components in diabetic nephropathy. Publicly available datasets for SLC5A2 (encoding SGLT-2) and complement system components were extracted specifically from microdissected tubulointerstitial (healthy controls: n = 31, diabetic nephropathy: n = 17) and glomerular compartments (healthy controls: n = 21, diabetic nephropathy: n = 12). First, we compared tubulointerstitial and glomerular log2 SLC5A2 mRNA expression levels and confirmed a predominant synthesis within the tubulointerstitial compartment. Among various complement components and receptors, the only significant finding was a positive association between SLC5A2 and the tubulointerstitial synthesis of the complement component C5 in diabetic nephropathy (p = 0.0109). Finally, intrarenal expression of SLC5A2 was associated predominantly with pathways involved in metabolic processes. Interestingly, intrarenal complement C5 synthesis was also associated with enrichment of metabolic signaling pathways, overlapping with SLC5A2 for “metabolism” and “biological oxidations”. These observations could be of relevance in the pathogenesis of diabetic nephropathy and implicate a mechanistic link between SGLT-2 and intrarenal complement synthesis.Open-Access-Publikationsfonds 202
Myositis
No full textThe S2e guidelines on myositis were completely updated and revised under the leadership of the German Society for Neurology and the participation of many other specialist societies. Immune-mediated necrotizing myopathy and antisynthetase syndrome are now regarded as independent entities in the classification of myositis. With respect to the diagnostics, the guidelines provide concrete recommendations on dysphagia screening, especially for inclusion body myositis and for cancer diagnostics in certain forms of myositis. Following the positive ProDERM study, the use of intravenous immunoglobulins (Octagam®) is available for treatment as an approved substance. Based on the INBUILD study, antifibrotic treatment with nintedanib is available for progressive fibrosing pulmonary involvement. For rheumatologists, the updated guidelines represent a document relevant for daily practice with many recommendations for the treatment of patients with myositis
A Transcriptome Array-Based Approach Links Proteinuria and Distinct Molecular Signatures to Intrarenal Expression of Type I Interferon IFNA5 in Lupus Nephritis
No full textIn systemic lupus erythematosus (SLE), the relevance of non-hematopoietic sources of type I interferon in human autoimmunity has recently been recognized. Particularly, type I interferon production precedes autoimmunity in early skin lesions related to SLE. However, the relevance of intrarenal type I interferon expression has not been shown in lupus nephritis. From transcriptome array datasets, median-centered log2 mRNA expression levels of IFNα (IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, and IFNA21), IFNω (IFNW1), and IFNβ (IFNB1) in lupus nephritis were extracted specifically from microdissected tubulointerstitial (n = 32) and glomerular compartments (n = 32). We found an association between proteinuria and tubulointerstitial expression of type I interferon IFNA5 (p = 0.0142), while all others were not significantly associated. By contrast, no such correlation was observed between proteinuria and any type I interferon expression in the glomerular compartment in lupus nephritis. Interestingly, there was no difference between female and male patients (p = 0.8237) and no association between type I interferon IFNA5 expression and kidney function or lupus nephritis progression. Finally, we identified distinct molecular signatures involved in transcriptional regulation (GLI protein-regulated transcription, IRF7 activation, and HSF1-dependent transactivation) and receptor signaling (BMP signaling and GPCR ligand binding) in association with tubulointerstitial expression of type I interferon IFNA5 in the kidney. In summary, this transcriptome array-based approach links proteinuria to the tubulointerstitial expression of type I interferon IFNA5 in lupus nephritis. Because type I interferon receptor subunit I antagonism has recently been investigated in active SLE, the current study further emphasizes the role of type I interferons in lupus nephritis and might also be of relevance for mechanistic studies.
Keywords: lupus nephritis; type I interferon; IFNA5; proteinuriaOpen Access Publication Funds of the Göttingen Universit
Avacopan improves patient perspective on steroid-related toxicity effects in a case with ANCA-associated vasculitis
No full textOpen-Access-Publikationsfonds 202
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