[Lung involvement in autoinflammatory diseases]. / Atteinte pulmonaire dans les maladies auto-inflammatoires.

Genetic autoinflammatory diseases are now a recognized and rapidly expanding group. The lung involvement historically associated with autoinflammatory diseases is inflammatory seritis, primarily seen in familial Mediterranean fever and other interleukin-1 mediated diseases. Over the last ten years, pulmonary involvement has been the core presentation of two autoinflammatory diseases associated with constitutive type I interferon activation, i.e. SAVI and COPA syndrome. Most patients with these diseases usually develop early progression to pulmonary fibrosis, which is responsible for high rates of morbidity and mortality. Other rare autoinflammatory diseases are associated with alveolar proteinosis, particularly when related to MARS mutations. Additionally, in adults, VEXAS is frequently associated with pulmonary involvement, albeit without prognosis effect. A molecular approach to autoinflammatory diseases enables not only the definition of biomarkers for diagnosis, but also the identification of targeted treatments. Examples include JAK inhibitors in SAVI and COPA syndrome, even though this therapy does not prevent progression to pulmonary fibrosis. Another illustrative example is the efficacy of methionine supplementation in alveolar proteinosis linked to MARS mutations. Overall, in autoinflammatory diseases the lung is now emerging as a possible affected organ. Continuing discovery of new autoinflammatory diseases is likely to uncover further pathologies involving the lung. Such advances are expected to lead to the development of novel therapeutic perspectives.

Two pediatric cases of multisystem inflammatory-like syndrome following COVID-19 vaccination.

Multisystem inflammatory syndrome in children (MIS-C) is a novel post-infectious disease occurring in the context of SARS-CoV2 infection. COVID-19 vaccines have been authorized since December 2020, and adverse events including myocarditis have been reported following vaccination. We describe the cases of two pediatric patients presenting with clinical and laboratory features suggestive of MIS-C a few days after receiving their first dose of the Pfizer BNT162b2 vaccine. The outcome was favorable for both patients (after corticosteroid and immunoglobulin administration for one patient). These cases suggest an association between the COVID-19 vaccine and the occurrence of MIS-C.

[When to consider type I interferonopathy in adulthood?] / Quand penser à une interféronopathie de type I chez l'adulte ?

Type I interferonopathies (IP1) are a heterogeneous group of Mendelian diseases characterized by overactivation of the type I interferon (IFN) pathway. They are caused by monogenic (rarely digenic) mutations of proteins involved in this key pathway of innate immunity. IP1 transmission can be dominant, recessive or X-linked and penetrance differs from one IP1 to another. The clinical spectrum is broad and mainly includes central nervous system involvement with calcifications of the basal ganglia, skin disorders such as cutaneous vasculitis that can be mutilating. Joint disorders including non-destructive deforming arthropathy, pulmonary involvement such as intra-alveolar haemorrhage or interstitial lung disease, and haematological symptoms with cytopenia and/or immune deficiency are also seen. The clinical manifestations vary from one IP1 to another and their spectrum is constantly expanding along with the description of new IP1s and patients. The inflammatory syndrome is generally mild and autoimmune stigmata are frequently found. Almost all patients display overexpression of the type I IFN pathway detected, for instance, by the evaluation of IFN-stimulated genes expression, referred as "interferon signature". The related morbidity and mortality are high. However, the beneficial effect on certain symptoms of targeted therapies inhibiting type I IFN, such as JAK inhibitors, has led to a promising improvement in the management of these patients.

Next-Generation Sequencing for Diagnosis and Tailored Therapy: A Case Report of Astrovirus-Associated Progressive Encephalitis.

A boy with X-linked agammaglobulinemia experienced progressive global motor decline, cerebellar syndrome, and epilepsy. All standard polymerase chain reactions for neurotropic viruses were negative on cerebrospinal fluid and brain biopsy. Next-generation sequencing allowed fast identification of a new astrovirus strain (HAstV-VA1/HMO-C-PA), which led to tailor the patient's treatment, with encouraging clinical monitoring over 1 year.