An immunogenomic exome landscape of triple positive primary antiphospholipid patients.

Primary antiphospholipid syndrome is characterized by thrombosis and autoantibodies directed against phospholipids or associated proteins. The genetic etiology of PAPS remains unknown. We enrolled 21 patients with thromboembolic events associated to lupus anticoagulant, anticardiolipin and anti ß2 glycoprotein1 autoantibodies. We performed whole exome sequencing and a systematic variant-based analysis in genes associated with thrombosis, in candidate genes previously associated with APS or inborn errors of immunity. Data were compared to public databases and to a control cohort of 873 non-autoimmune patients. Variants were identified following a state-of-the-art pipeline. Enrichment analysis was performed by comparing with the control cohort. We found an absence of significant HLA bias and genetic heterogeneity in these patients, including when testing combinations of rare variants in genes encoding for proteins involved in thrombosis and of variants in genes linked with inborn errors of immunity. These results provide evidence of genetic heterogeneity in PAPS, even in a homogenous series of triple positive patients. At the individual scale, a combination of variants may participate to the breakdown of B cell tolerance and to the vessel damage.

Systematic toxicity investigation of graphene oxide: evaluation of assay selection, cell type, exposure period and flake size.

Understanding the toxicity of nanomaterials is essential for the safe and sustainable development of new applications. This is particularly true for a nanomaterial as widely used as graphene oxide (GO), which is utilized as films for electronics, membranes for filtration, drug carriers and more. Despite this, the current literature presents conflicting results on the overall toxicity of GO. Here, the cytotoxicity of three sizes of commercially available GO was investigated on six cell lines, as values of NOAEL/LOAEL. The effectiveness of four viability assays was also evaluated. The overall toxicity of GO greatly varied between cell lines; the suspension cells showed a greater response to the GO treatment compared to the adherent cell lines. Time dependent cytotoxicity was also cell line dependent, with only one cell line demonstrating obvious dependence. The six cell lines were also tested to evaluate their response to varying GO flake sizes: the suspension/phagocytic cells showed little variation in viability, while a difference was observed for the adherent/non-phagocytic cell lines. By systematically studying the effect of dose, GO size and treatment time for the six cell lines by using commercially available GO samples, we eliminate many of the variables which may result in the conflicting reports on the cytotoxicity of GO in the literature.

[Primary immunodeficiency and autoimmunity]. / Déficit immunitaire primitif de l'adulte et auto-immunité.

Many evidences highlight that immunodeficiency and autoimmunity are two sides of a same coin. Primary immune deficiencies (PIDs), which are rare mono- or multigenic defects of innate or adaptative immunity, frequently associate with autoimmunity. Analyses of single-gene defects in immune pathways of families with PIDs, by new tools of molecular biology (next genome sequencing technologies), allowed a better understanding of the ways that could both drive immune defect with immune deficiency and autoimmunity. Moreover, genes implicated in rare single-gene defects are now known to be also involved in polygenic conventional autoimmune diseases. Here, we describe the main autoimmune symptoms occurring in PIDs and the underlying mechanisms that lead to autoimmunity in immunodeficiency. We review the links between autoimmunity and immunodeficiency and purpose some principles of care for patients with PIDs and autoimmunity.

Leprosy in a pregnant woman.

Herein, we describe a case of leprosy in a 29-year-old pregnant southeast-asian woman who presented with joint pain and multiple disseminated erythematous macules, papules and plaques. Histological examination and stains for acid-fast bacilli from skin biopsies substantiated the clinical suspicion of a cutaneous mycobacterial disease and both should be performed in all patients with unidentified skin lesions. The definitive laboratory diagnosis of leprosy was achieved by the application of a species-specific real-time polymerase chain reaction from infected tissue.