[Connective tissue disease-related interstitial lung disease]. / Pneumopathie interstitielle secondaire aux connectivites.

The connectivitides are autoimmune diseases that affect many organs. All of them can cause interstitial lung disease, the most frequent forms being the NSIP (nonspecific interstitial pneumonia) and the UIP (usual interstitial pneumonia). The best screening method is the high-resolution chest CT. The treatment of ILD includes glucocorticoids, immunosuppressive and antifibrotic agents, as well as non-pharmacological therapies. We present the screening and treatment algorithm for the ILD in systemic sclerosis, which is very well established. We also discuss the management of the ILD in rheumatoid arthritis, a very prevalent disease, and though of large public interest.

Les connectivites sont des maladies autoimmunes touchant différents organes. Toutes peuvent causer une pneumopathie interstitielle (Interstitial Lung Disease (ILD)), les formes les plus fréquentes étant la Nonspecific Interstitial Pneumonia et l'Usual Interstitial Pneumonia. La meilleure méthode de dépistage est le CT-scan à haute résolution. Le traitement de l'ILD repose sur les glucocorticoïdes, les immunosuppresseurs et les antifibrotiques, ainsi que sur des mesures non médicamenteuses. Nous détaillerons l'algorithme de dépistage et de traitement de l'ILD associée à la sclérodermie systémique, car il est le mieux défini. Nous discuterons également de celui de l'ILD associée à la polyarthrite rhumatoïde, maladie qui est très fréquente et donc d'intérêt majeur.

Familial Mediterranean fever mutations are hypermorphic mutations that specifically decrease the activation threshold of the Pyrin inflammasome.

Objectives: FMF is the most frequent autoinflammatory disease and is associated in most patients with bi-allelic MEFV mutations. MEFV encodes Pyrin, an inflammasome sensor activated following RhoGTPase inhibition. The functional consequences of MEFV mutations on the ability of Pyrin variants to act as inflammasome sensors are largely unknown. The aim of this study was to assess whether MEFV mutations affect the ability of Pyrin to detect RhoGTPase inhibition and other inflammasome stimuli. Methods: IL-1ß and IL-18 released by monocytes from healthy donors (HDs) and FMF patients were measured upon specific engagement of the Pyrin, NLRP3 and NLRC4 inflammasomes. Cell death kinetics following Pyrin activation was monitored in real time. Results: Monocytes from FMF patients secreted significantly more IL-1ß and IL-18 and died significantly faster than HD monocytes in response to low concentrations of Clostridium difficile toxin B (TcdB), a Pyrin-activating stimulus. Monocytes from patients bearing two MEFV exon 10 pathogenic variants displayed an increased Pyrin inflammasome response compared with monocytes from patients with a single exon 10 pathogenic variant indicating a gene-dosage effect. Using a short priming step, the response of monocytes from FMF patients to NLRP3- and NLRC4-activating stimuli was normal indicating that MEFV mutations trigger a specific hypersensitivity of monocytes to low doses of a Pyrin-engaging stimulus. Conclusion: Contrary to the NLRP3 mutations described in cryopyrin-associated periodic syndrome, FMF-associated MEFV mutations do not lead to a constitutive activation of Pyrin. Rather, FMF-associated mutations are hypermorphic mutations that specifically decrease the activation threshold of the Pyrin inflammasome without affecting other canonical inflammasomes.