Clinico-pathological considerations in a 48-years-old female with acute kidney injury: is it lupus nephritis, ANCA-associated vasculitis or something else?

BACKGROUND: The value of ANCA positivity in the setting of systemic lupus erythematous and their pathogenicity remains uncertain. CASE PRESENTATION: We report the case of a 48-year-old female with rapidly progressive kidney failure, arthro-myalgia and weight loss. Auto-immune screening showed anti-dsDNA antibodies, complement consumption and triple ANCA positivity. A first kidney biopsy done at presentation highlighted class IV-G glomerulonephritis with elective extra-capillary involvement and mainly C1q glomerular deposition at immunofluorescence study. After three months of a regimen combining steroids and cyclophosphamide, a second biopsy was performed and showed class IV-G glomerulonephritis with mainly endocapillary proliferation. CONCLUSION: This case is atypical in view of immunological profile and kidney histopathological presentation and evolution and gives rise to discussion in view of recent data on ANCA value in lupus nephritis, and suggests that different auto-immune pathways may be involved in lupus nephritis

Mycolactone as Analgesic: Subcutaneous Bioavailability Parameters

is the bacillus responsible for Buruli ulcer, an infectious disease and the third most important mycobacterial disease worldwide, after tuberculosis and leprosy. infection is a type of panniculitis beginning mostly with a nodule or an oedema, which can progress to large ulcerative lesions. The lesions are caused by mycolactone, the polyketide toxin of . Mycolactone plays a central role for host colonization as it has immunomodulatory and analgesic effects. On one hand, mycolactone induces analgesia by targeting type-2 angiotensin II receptors (ATR), causing cellular hyperpolarization and neuron desensitization. Indeed, a single subcutaneous injection of mycolactone into the mouse footpad induces a long-lasting hypoesthesia up to 48 h. It was suggested that the long-lasting hypoesthesia may result from the persistence of a significant amount of mycolactone locally following its injection, which could be probably due to its slow elimination from tissues. To verify this hypothesis, we investigated the correlation between hypoesthesia and mycolactone bioavailability directly at the tissue level. Various quantities of mycolactone were then injected in mouse tissue and hypoesthesia was recorded with nociception assays over a period of 48 h. The hypoesthesia was maximal 6 h after the injection of 4 μg mycolactone. The basal state was reached 48 h after injection, which demonstrated the absence of nerve damage. Surprisingly, mycolactone levels decreased strongly during the first hours with a reduction of 70 and 90% after 4 and 10 h, respectively. Also, mycolactone did not diffuse in neighboring skin tissue and only poorly into the bloodstream upon direct injection. Nevertheless, the remaining amount was sufficient to induce hypoesthesia during 24 h. Our results thus demonstrate that intact mycolactone is rapidly eliminated and that very small amounts of mycolactone are sufficient to induce hypoesthesia. Taken together, our study points out that mycolactone ought to be considered as a promising analgesic

Myopathy caused by anoctamin 5 mutations and necrotizing vasculitis

International audienc

Pre-transplant CD45RC expression on blood T cells differentiates patients with cancer and rejection after kidney transplantation

Background Biological biomarkers to stratify cancer risk before kidney transplantation are lacking. Several data support that tumor development and growth is associated with a tolerant immune profile. T cells expressing low levels of CD45RC preferentially secrete regulatory cytokines and contain regulatory T cell subset. In contrast, T cells expressing high levels of CD45RC have been shown to secrete proinflammatory cytokines, to drive alloreactivity and to predict acute rejection (AR) in kidney transplant patients. In the present work, we evaluated whether pre-transplant CD45RClow T cell subset was predictive of post-transplant cancer occurrence. Methods We performed an observational cohort study of 89 consecutive first time kidney transplant patients whose CD45RC T cell expression was determined by flow cytometry before transplantation. Post-transplant events including cancer, AR, and death were assessed retrospectively. Results After a mean follow-up of 11.1±4.1 years, cancer occurred in 25 patients (28.1%) and was associated with a decreased pre-transplant proportion of CD4+CD45RChigh T cells, with a frequency below 51.9% conferring a 3.7-fold increased risk of post-transplant malignancy (HR 3.71 [1.24–11.1], p = 0.019). The sensibility, specificity, negative predictive and positive predictive values of CD4+CD45RChigh<51.9% were 84.0, 54.7, 89.8 and 42.0% respectively. Confirming our previous results, frequency of CD8+CD45RChigh T cells above 52.1% was associated with AR, conferring a 20-fold increased risk (HR 21.7 [2.67–176.2], p = 0.0004). The sensibility, specificity, negative predictive and positive predictive values of CD8+CD45RChigh>52.1% were 94.5, 68.0, 34.7 and 98.6% respectively. Frequency of CD4+CD45RChigh T cells was positively correlated with those of CD8+CD45RChigh (p<0.0001), suggesting that recipients with high AR risk display a low cancer risk. Conclusion High frequency of CD45RChigh T cells was associated with AR, while low frequency was associated with cancer. Thus, CD45RC expression on T cells appears as a double-edged sword biomarker of promising interest to assess both cancer and AR risk before kidney transplantation

Sunlight-induced phototransformation of transphilic and hydrophobic fractions of Suwannee River dissolved organic matter.

Sunlight-induced chemical changes of both transphilic (SWR-TPH) and hydrophobic (SWR-HPO) fractions of Suwannee River dissolved organic matter (DOM) were followed by ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS). Irradiated SWR-TPH exhibited increase of chemodiversity, loss of some aromatic compounds, and almost no change in terms of average values of m/z, O/C and double bond equivalents (DBE). Irradiated SWR-HPO showed decrease of chemodiversity, average values of m/z, O/C and DBE. Irradiation of SWR-HPO produced oxygenated (O/C > 0.7) and aliphatic new compounds and removed some aromatics and carboxyl-rich alicyclic molecules (CRAM). Comparatively, CHO-compounds of SWR-TPH were relatively stable with a minor class of aromatic compounds disappeared under sunlight irradiation. Photochemical processing of SWR-HPO generated highly oxygenated new compounds that were readily present in SWR-TPH, implying that sunlight changes the hydrophobicity of DOM and that SWR-HPO is a photochemical precursor for SWR-TPH. This study contributed to the developing knowledge on organic matter phototransformation, particularly the transformation pattern of SWR-TPH that was never described previously; it also demonstrated the role of sunlight in producing SWR-TPH compounds from SWR-HPO and consequently driving the transformation of organic matter

High pressure membrane foulants of seawater, brackish water and river water: Origin assessed by sugar and bacteriohopanepolyol signatures

The present work aimed to study the origin of foulant material recovered on membranes used in water treatment. Firstly, sugar signatures were assessed from the monosaccharide composition. As results were not conclusive, a statistical approach using discriminant analysis was applied to the sugar data set in order to predict the origin of the foulant material. Three groups of various origins (algal, microbial, continental dissolved organic matter) were used as sugar references for the prediction. The results of the computation showed that the origin of reverse osmosis (RO) seawater foulant material is influenced by both the location of the water sources and the season. RO brackish water and nanofiltration river water foulant materials had a terrestrial origin. Secondly, bacteriohopanepolyol signatures indicated that RO seawater foulant material had a marine signature, RO brackish water foulant material had both a marine and a terrestrial origin and the nanofiltration river water foulant material contained only a terrestrial signature