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Maintenance of cell proteostasis relies on two degradation pathways: proteasome and autophagy. Here we describe a new proteostasis pathway avoiding degradation of abnormal proteins yet carrying them outside the cell using nanovesicles called myelinosomes. These myelinosomes are produced in pathological or stress situations in relation with genetic or environmental factors. Myelinosome vesicles are nano-sized multi-stacked membrane structures, resembling myelin sheath. It has recently been shown in two models of genetic diseases (Huntington's disease and cystic fibrosis) that myelinosomes are important for eliminating mutant proteins in an unusual secretory process, thus preventing their accumulation and aggregation in cells.Les myélinosomes : une nouvelle voie du contrôle de qualité des protéines.Deux voies de dégradation des protéines mal repliées sont classiquement décrites : la voie du protéasome et la voie de l’autophagie. Nous décrivons ici une nouvelle voie de protéostase cellulaire ne dégradant pas la protéine anormale mais l’expulsant hors de la cellule grâce à des nanovésicules appelées myélinosomes. Ces myélinosomes sont produits par la cellule dans des situations pathologiques ou de stress en lien avec des facteurs génétiques ou environnementaux. Sur le plan morphologique, les myélinosomes sont caractérisés par des membranes osmiophiles denses aux électrons dont l’arrangement empilé est semblable à celui de la myéline et présente jusqu’à 30 feuillets selon le type de cellule. Dans deux modèles, au moins, de maladies génétiques (la maladie de Huntington et la mucoviscidose), les myélinosomes sont importants pour éliminer les protéines mutées par un processus sécrétoire inhabituel, évitant ainsi leur agrégation dans les cellules.

INTRODUCTION : La maladie des dépôts de chaînes légères d’immunoglobuline est une entité anatomoclinique entraînant, dans de rares cas, une destruction kystique du poumon. OBSERVATION : Nous rapportons le cas d’une patiente de 62 ans, suivie dans le cadre d’une gammapathie monoclonale de signification indéterminée, chez qui, suite à l’apparition d’une dyspnée croissante, des lésions pulmonaires kystiques diffuses sont découvertes au scanner thoracique. Une résection par thoracoscopie du lobe inférieur droit où prédominait l’atteinte kystique a permis le diagnostic histologique de maladie des dépôts de chaînes légères kappa non amyloïdes. La chirurgie a également eu un effet de réduction de volume pulmonaire s’accompagnant d’une amélioration clinique et fonctionnelle via l’amélioration de la ventilation des segments voisins. CONCLUSION : Cette observation de maladie des dépôts de chaînes légères avec atteinte kystique pulmonaire illustre les potentiels bénéfices cliniques et fonctionnels observés après chirurgie de réduction pulmonaire. [Effect of surgery of pulmonary cysts related to immunoglobulin light chain deposits] INTRODUCTION: Light chain deposition disease is a rare anatomo-clinical disorder, which rarely leads to cystic lung destruction. CASE REPORT: We report the case of a 62years old female patient with a history of a monoclonal gammopathy of unknown significance who developed progressive dyspnea. Thoracic CT-scan demonstrated a diffuse pulmonary cystic disorder with predominance in the right lower lobe. Thoracoscopic surgical resection of that lobe led to a diagnosis of non-amyloid kappa light chain deposits. Surgery also resulted in a lung volume reduction effect with clinical and functional benefits related to improved ventilation of adjacent segments. CONCLUSION: This report of pulmonary cystic disorder related to a light chain deposition disease highlights the potential clinical and functional benefits observed after lung volume reduction surgery.

Light chain deposition disease is a rare anatomo-clinical disorder, which rarely leads to cystic lung destruction.We report the case of a 62years old female patient with a history of a monoclonal gammopathy of unknown significance who developed progressive dyspnea. Thoracic CT-scan demonstrated a diffuse pulmonary cystic disorder with predominance in the right lower lobe. Thoracoscopic surgical resection of that lobe led to a diagnosis of non-amyloid kappa light chain deposits. Surgery also resulted in a lung volume reduction effect with clinical and functional benefits related to improved ventilation of adjacent segments.This report of pulmonary cystic disorder related to a light chain deposition disease highlights the potential clinical and functional benefits observed after lung volume reduction surgery.

Huntington's disease is a rare neurodegenerative disease caused by a pathologic CAG expansion in the exon 1 of the huntingtin (HTT) gene. Aggregation and abnormal function of the mutant HTT (mHTT) cause motor, cognitive and psychiatric symptoms in patients, which lead to death in 15-20 years. Currently, there is no treatment for HD. Experimental approaches based on drug, cell or gene therapy are developed and reach progressively to the clinic. Among them, mHTT silencing using small non-coding nucleic acids display important physiopathological benefit in HD experimental models.

Immunoglobulin A (IgA) nephropathy (N) is the most common form of primary glomerulonephritis in the world and one of the first cause of end-stage renal failure. IgAN is characterized by the accumulation in mesangial areas of immune complexes containing IgA1. While epidemiology and clinical studies of IgAN are well-established, the mechanism(s) underlying disease development is poorly understood. The pathogenesis of this disease involves the deposition of polymeric and undergalactosylated IgA1 in the mesangium. Quantitative and structural changes of IgA1 play a key role in the development of the disease, due to functional abnormalities of two IgA receptors: the FcαR (CD89) expressed by blood myeloid cells and the transferrin receptor (TfR1) on mesangial cells. Abnormal IgA induces release of soluble CD89, responsible for the formation of circulating IgA complexes. These complexes are trapped by the TfR1 that is overexpressed on mesangial cells in IgAN patients, inducing the expression of transglutaminase 2. This enzyme stabilises IgA deposits at the surface of mesangial cells. These cells are then activated, proliferate and produce proinflammatory cytokines, leading to the loss of renal function.