Prostaglandin D2 amplifies lupus disease through basophil accumulation in lymphoid organs.

In systemic lupus erythematosus (SLE), autoantibody production can lead to kidney damage and failure, known as lupus nephritis. Basophils amplify the synthesis of autoantibodies by accumulating in secondary lymphoid organs. Here, we show a role for prostaglandin D2 (PGD2) in the pathophysiology of SLE. Patients with SLE have increased expression of PGD2 receptors (PTGDR) on blood basophils and increased concentration of PGD2 metabolites in plasma. Through an autocrine mechanism dependent on both PTGDRs, PGD2 induces the externalization of CXCR4 on basophils, both in humans and mice, driving accumulation in secondary lymphoid organs. Although PGD2 can accelerate basophil-dependent disease, antagonizing PTGDRs in mice reduces lupus-like disease in spontaneous and induced mouse models. Our study identifies the PGD2/PTGDR axis as a ready-to-use therapeutic modality in SLE.

Basophils contribute to pristane-induced Lupus-like nephritis model.

Lupus nephritis (LN), one of the most severe outcomes of systemic lupus erythematosus (SLE), is initiated by glomerular deposition of immune-complexes leading to an inflammatory response and kidney failure. Autoantibodies to nuclear antigens and autoreactive B and T cells are central in SLE pathogenesis. Immune mechanisms amplifying this autoantibody production drive flares of the disease. We previously showed that basophils were contributing to LN development in a spontaneous lupus-like mouse model (constitutive Lyn -/- mice) and in SLE subjects through their activation and migration to secondary lymphoid organs (SLOs) where they amplify autoantibody production. In order to study the basophil-specific mechanisms by which these cells contribute to LN development, we needed to validate their involvement in a genetically independent SLE-like mouse model. Pristane, when injected to non-lupus-prone mouse strains, induces a LN-like disease. In this inducible model, basophils were activated and accumulated in SLOs to promote autoantibody production. Basophil depletion by two distinct approaches dampened LN-like disease, demonstrating their contribution to the pristane-induced LN model. These results enable further studies to decipher molecular mechanisms by which basophils contribute to lupus progression.

[Vascular steal syndrome due to the creation of an arteriovenous shunt for hemodialysis, patient information and nephrologist responsibility]. / Vol vasculaire secondaire à la création d'un shunt artérioveineux pour hémodialyse, information du patient et responsabilité du néphrologue.

Although responsibility is a fundamental determinant in medical practice, physicians are generally unfamiliar with its principles. The same is true for disclosure requirements and requests for compensation in the event of physical injury. We report on a representative survey of iatrogenic complications that may arise after the implementation of vascular access for haemodialysis and that illustrate's the physician's responsibility and obligation to inform the patient. Vascular access steal syndrome is a serious complication of arteriovenous fistulas, and physicians may not be sufficiently aware of the likelihood of its occurrence. Diabetes (via medial calcific sclerosis) and placement in the brachial artery (with excessively high flow rates) are the main risk factors. The precariousness of vascular status in dialysis patients threatens to increase the incidence of this complication. The therapeutic challenge is to resolve ischemic events while maintaining vascular access. The presence of gangrene of the fingers is a formal indication for surgery. The borderline between therapeutic risk (the risk inherent in a medical procedure and which cannot be controlled) and liability for injury is blurred. The French Patient's Rights Act (voted on March 4th, 2002) emphasizes the physician's duty to inform the patient of treatment-associated risks and the fact that the physician now bears the burden of proof. We suggest that a patient information sheet on the benefits and risks of vascular access should be published on the French Society of Nephrology, Dialysis and Transplantation's website.