Current Evidence Supporting the Role of Immune Response in ATTRv Amyloidosis

Hereditary transthyretin (ATTRv) amyloidosis with polyneuropathy, also known as familial amyloid polyneuropathy (FAP), represents a progressive, heterogeneous, severe, and multisystemic disease caused by pathogenic variants in the TTR gene. This autosomal-dominant neurogenetic disorder has an adult onset with variable penetrance and an inconstant phenotype, even among subjects carrying the same mutation. Historically, ATTRv amyloidosis has been viewed as a non-inflammatory disease, mainly due to the absence of any mononuclear cell infiltration in ex vivo tissues; nevertheless, a role of inflammation in its pathogenesis has been recently highlighted. The immune response may be involved in the development and progression of the disease. Fibrillary TTR species bind to the receptor for advanced glycation end products (RAGE), probably activating the nuclear factor κB (NF-κB) pathway. Moreover, peripheral blood levels of several cytokines, including interferon (IFN)-gamma, IFN-alpha, IL-6, IL-7, and IL-33, are altered in the course of the disease. This review summarizes the current evidence supporting the role of the immune response in ATTRv amyloidosis, from the pathological mechanisms to the possible therapeutic implications

A lower bound on intergalactic magnetic fields from time variability of 1ES 0229+200 from MAGIC and Fermi /LAT observations

Context. Extended and delayed emission around distant TeV sources induced by the effects of propagation of ? ray s through the intergalactic medium can be used for the measurement of the intergalactic magnetic field (IGMF). Aims. We search for delayed GeV emission from the hard-spectrum TeV ?-ray emitting blazar 1ES 0229+200, with the goal of detecting or constraining the IGMF-dependent secondary flux generated during the propagation of TeV ? rays through the intergalactic medium. Methods. We analysed the most recent MAGIC observations over a 5 year time span, and complemented them with historic data of the H.E.S.S. and VERITAS telescopes, along with a 12-year-long exposure of the Fermi/LAT telescope. We used them to trace source evolution in the GeV TeV band over a decade and a half. We used Monte Carlo simulations to predict the delayed secondary ?-ray flux, modulated by the source variability, as revealed by TeV-band observations. We then compared these predictions for various assumed IGMF strengths to all available measurements of the ?-ray flux evolution. Results. We find that the source flux in the energy range above 200 GeV experiences variations around its average on the 14-year time span of observations. No evidence for the flux variability is found in the 1100 GeV energy range accessible to Fermi/LAT. The non-detection of variability due to delayed emission from electromagnetic cascade developing in the intergalactic medium imposes a lower bound of B > 1.8 - 1017 G for the long-correlation-length IGMF and B > 1014 G for an IGMF of cosmological origin. Though weaker than the one previously derived from the analysis of Fermi/LAT data, this bound is more robust, being based on a conservative intrinsic source spectrum estimate and accounting for the details of source variability in the TeV energy band. We discuss implications of this bound for cosmological magnetic fields that might explain the baryon asymmetry of the Universe