Fibrillary glomerulonephritis and immunotactoid (microtubular) glomerulopathy are associated with distinct immunologic features

Fibrillary glomerulonephritis and immunotactoid (microtubular) glomerulopathy are associated with distinct immunologic features.BackgroundThe clinical relevance of distinguishing two types of glomerulonephritis (GN) with non-amyloid organized immunoglobulin (Ig) deposits—fibrillary GN (FGN) and immunotactoid (microtubular) GN (IT/MTGN)—on the basis of ultrastructural organization, is debated.MethodsTwenty-three patients with organized glomerular Ig deposits were classified into two groups based on the fibrillar or microtubular ultrastructural appearance of the deposits. Kidney biopsy samples were studied by immunofluorescence microscopy, using anti-light chain conjugates (all cases) and anti-IgG subclass conjugates (13 patients). In each group, we studied clinicopathological features, associated monoclonal gammapathy (detected by immunoelectrophoresis and/or immunoblot) or B-cell lymphoproliferative disease, effects of chemotherapy and long-term renal outcome.ResultsIn 14 IT/MTGN and 9 FGN patients, clinical symptoms [hypertension, nephrotic syndrome (NS) and hematuria] and the mean diameters of the substructures were similar. In 13 IT/MTGN patients, glomerular (IgG1, 2 or 3) deposits were monotypic (κ, 7 cases; λ, 6 cases). Glomerular deposits were associated with a monoclonal Ig of the same isotype in eight patients, detected in the serum (5 cases), and/or in the cytoplasm of lymphocytes (4 cases), and with lymphoproliferative disease in seven patients. The ultrastructural features of monoclonal Ig inclusions in lymphocytes were similar to those of glomerular microtubular deposits. In contrast, none of the FGN patients presented lymphoplasmocytic proliferation or paraproteinemia. Glomerular Ig deposits were polyclonal in eight cases and contained IgG4 in all three cases studied. Although patient and renal survival did not differ significantly between the two groups, chemotherapy led to remission of NS in ten IT/MTGN patients, with parallel improvement in hematological parameters.ConclusionsThe identification of ultrastructural patterns in these nephropathies is important. GN with organized microtubular monoclonal deposits (GOMMID) probably accounts for a large proportion of immunotactoid (microtubular) GN cases

The ABA-Deficiency Suppressor Locus HAS2 Encodes the PPR Protein LOI1/MEF11 Involved in Mitochondrial RNA Editing

The hot ABA-deficiency suppressor2 (has2) mutation increases drought tolerance and the ABA sensitivity of stomata closure and seed germination. Here we report that the HAS2 locus encodes the MITOCHONDRIAL EDITING FACTOR11 (MEF11), also known as LOVASTATIN INSENSITIVE1. has2/mef11 mutants exhibited phenotypes very similar to the ABA-hypersensitive mutant, hai1-1 pp2ca-1 hab1-1 abi1-2, which is impaired in four genes encoding type 2C protein phosphatases (PP2C) that act as upstream negative regulators of the ABA signaling cascade. Like pp2c, mef11 plants were more resistant to progressive water stress and seed germination was more sensitive to paclobutrazol (a gibberellin biosynthesis inhibitor) as well as mannitol and NaCl, compared with the wild-type plants. Phenotypic alterations in mef11 were associated with the lack of editing of transcripts for the mitochondrial cytochrome c maturation FN2 (ccmFN2) gene, which encodes a cytochrome c-heme lyase subunit involved in cytochrome c biogenesis. Although the abundance of electron transfer chain complexes was not affected, their dysfunction could be deduced from increased respiration and altered production of hydrogen peroxide and nitric oxide in mef11 seeds. As minor defects in mitochondrial respiration affect ABA signaling, this suggests an essential role for ABA in mitochondrial retrograde regulation

Tubulo-interstitial nephritis with Fanconi syndrome in Behçet disease.

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Analysis of xyloglucan metabolism mutants highlights the prominent role of xylose cleavage in seed dormancy

International audienceSeed dormancy is an adaptive trait that delays germination until environmental conditions become favorable for seedling survival and growth. Germination has been shown to depend on the mechanical resistance strength of the covering layers (testa and endosperm) that counteracts the growth force of the embryo. Cell wall remodeling is essential in the regulation of germination processes. In Arabidopsis thaliana, the side chain trimming of xyloglucans (XyG), the major hemicellulose in cell walls, by the apoplastic XYLOSIDASE1 (XYL1), has been previously shown to regulate XyG side chain length and seed dormancy. To investigate to what extent side chain complexity impacts on cell wall mechanical properties and regulates seed germination, xyl1 mutations were combined here with mutations in the two other glycosidases, the fucosidase AXY8 and the beta‐galactosidase BGAL10. Analysis of germination phenotypes in axy8 bgal10 xyl1 and in several XyG biosynthesis mutants did not show any link between dormancy depth and side chain length. The very specific effect of xyl1 on seed dormancy in single and multiple mutants was clearly correlated with alterations in XyG intracellular localization, together with release and oxidation of free oligosaccharides (XGO). Accumulation of oxidized XGO could negatively impact cell wall remodeling by impairing remobilization and polarized secretion in cell walls, thus reducing growth anisotropy in elongating organs and modifying mechanical characteristics in seed tissues

Low incidence of SARS-CoV-2, risk factors of mortality and the course of illness in the French national cohort of dialysis patients

International audienceThe aim of this study was to estimate the incidence of COVID-19 disease in the French national population of dialysis patients, their course of illness and to identify the risk factors associated with mortality. Our study included all patients on dialysis recorded in the French REIN Registry in April 2020. Clinical characteristics at last follow-up and the evolution of COVID-19 illness severity over time were recorded for diagnosed cases (either suspicious clinical symptoms, characteristic signs on the chest scan or a positive reverse transcription polymerase chain reaction) for SARS-CoV-2. A total of 1,621 infected patients were reported on the REIN registry from March 16th, 2020 to May 4th, 2020. Of these, 344 died. The prevalence of COVID-19 patients varied from less than 1% to 10% between regions. The probability of being a case was higher in males, patients with diabetes, those in need of assistance for transfer or treated at a self-care unit. Dialysis at home was associated with a lower probability of being infected as was being a smoker, a former smoker, having an active malignancy, or peripheral vascular disease. Mortality in diagnosed cases (21%) was associated with the same causes as in the general population. Higher age, hypoalbuminemia and the presence of an ischemic heart disease were statistically independently associated with a higher risk of death. Being treated at a selfcare unit was associated with a lower risk. Thus, our study showed a relatively low frequency of COVID-19 among dialysis patients contrary to what might have been assumed