ANCA-associated vasculitis.

The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are a group of disorders involving severe, systemic, small-vessel vasculitis and are characterized by the development of autoantibodies to the neutrophil proteins leukocyte proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA). The three AAV subgroups, namely granulomatosis with polyangiitis (GPA), microscopic polyangiitis and eosinophilic GPA (EGPA), are defined according to clinical features. However, genetic and other clinical findings suggest that these clinical syndromes may be better classified as PR3-positive AAV (PR3-AAV), MPO-positive AAV (MPO-AAV) and, for EGPA, by the presence or absence of ANCA (ANCA+ or ANCA-, respectively). Although any tissue can be involved in AAV, the upper and lower respiratory tract and kidneys are most commonly and severely affected. AAVs have a complex and unique pathogenesis, with evidence for a loss of tolerance to neutrophil proteins, which leads to ANCA-mediated neutrophil activation, recruitment and injury, with effector T cells also involved. Without therapy, prognosis is poor but treatments, typically immunosuppressants, have improved survival, albeit with considerable morbidity from glucocorticoids and other immunosuppressive medications. Current challenges include improving the measures of disease activity and risk of relapse, uncertainty about optimal therapy duration and a need for targeted therapies with fewer adverse effects. Meeting these challenges requires a more detailed knowledge of the fundamental biology of AAV as well as cooperative international research and clinical trials with meaningful input from patients

Immunological and translational key challenges in systemic lupus erythematosus: A symposium update.

The first LBMR-Tim (Toulouse Referral Medical Laboratory of Immunology) symposium convened on December 16, 2022 in Toulouse, France to address challenging questions in systemic lupus erythematosus (SLE). Special focus was put on (i) the role played by genes, sex, TLR7, and platelets on SLE pathophysiology; (ii) autoantibodies, urinary proteins, and thrombocytopenia contribution at the time of diagnosis and during follow-up; (iii) neuropsychiatric involvement, vaccine response in the COVID-19 era, and lupus nephritis management at the clinical frontline; and (iv) therapeutic perspectives in patients with lupus nephritis and the unexpected adventure of the Lupuzor/P140 peptide. The multidisciplinary panel of experts further supports the concept that a global approach including basic sciences, translational research, clinical expertise, and therapeutic development have to be prioritized in order to better understand and then improve the management of this complex syndrome

BONE Sarcoidosis: A French Case Control Study

International audienc

Soluble CD95L (FasL) stimulates ROS-production in Neutrophils and contributes to the pathology progression in ANCA-Associated Vasculitis

International audienc

Soluble CD95L (FasL) stimulates ROS-production in Neutrophils and contributes to the pathology progression in ANCA-Associated Vasculitis

International audienc

JCI Insight

Tregs are impaired in human systemic lupus erythematosus (SLE) and contribute to effector T cell activation. However, the mechanisms responsible for the Treg deficiency in SLE remain unclear. We hypothesized that the OX40L/OX40 axis is implicated in Treg and regulatory follicular helper T (Tfr) cell dysfunction in human SLE. OX40L/OX40 axis engagement on Tregs and Tfr cells not only specifically impaired their ability to regulate effector T cell proliferation, but also their ability to suppress T follicular helper (Tfh) cell-dependent B cell activation and immunoglobulin secretion. Antigen-presenting cells from patients with active SLE mediated Treg dysfunction in an OX40L-dependent manner, and OX40L-expressing cells colocalized with Foxp3+ cells in active SLE skin lesions. Engagement of the OX40L/OX40 axis resulted in Foxp3 downregulation in Tregs, and expression in SLE Tregs correlated with the proportion of circulating OX40L-expressing myeloid DCs. These data support that OX40L/OX40 signals are implicated in Treg dysfunction in human SLE. Thus, blocking the OX40L/OX40 axis appears to be a promising therapeutic strategy