I Muscari

Biological treatments: new weapons in the management of monogenic autoinflammatory disorders

Treatment of monogenic autoinflammatory disorders, an expanding group of hereditary diseases characterized by apparently unprovoked recurrent episodes of inflammation, without high-titre autoantibodies or antigen-specific T cells, has been revolutionized by the discovery that several of these conditions are caused by mutations in proteins involved in the mechanisms of innate immune response, including components of the inflammasome, cytokine receptors, receptor antagonists, and oversecretion of a network of proinflammatory molecules. Aim of this review is to synthesize the current experience and the most recent evidences about the therapeutic approach with biologic drugs in pediatric and adult patients with monogenic autoinflammatory disorders.

The diagnostic evaluation of patients with potential adult-onset autoinflammatory disorders: Our experience and review of the literature

Hereditary periodic fever syndromes (HPFSs) are a group of inherited disorders of the innate immune system caused by mutations of genes involved in the regulation or activation of the inflammatory response, which belong to the category of autoinflammatory disorders. Most HPFs typically have an onset in pediatric age, while a limited number of patients experience disease onset during adulthood. The relative rarity and lack of information on adult-onset autoinflammatory diseases make it likely that genetic testing is often inconclusive. Recently, we have identified a set of variables related to the probability of detecting gene mutations in MEFV, responsible for familial Mediterranean fever, and TNFRSF1A, responsible for tumor necrosis factor receptor-associated periodic syndrome. In addition, we have proposed a diagnostic score for identifying those patients at high risk of carrying mutations in these genes. However, before the score can be recommended for application, further evaluation by means of longitudinal studies on different ethnicities and different populations deriving from other geographical areas is needed in order to definitively verify both its sensitivity and its specificity. The present manuscript offers our suggestions on how to establish a differential diagnosis for adult-onset HPFs, as well as a review of the literature, and we also provide a score revision available online.

First Report of Circulating MicroRNAs in Tumour Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS)

Tumor necrosis factor-receptor associated periodic syndrome (TRAPS) is a rare autosomal dominant autoinflammatory disorder characterized by recurrent episodes of long-lasting fever and inflammation in different regions of the body, such as the musculo-skeletal system, skin, gastrointestinal tract, serosal membranes and eye. Our aims were to evaluate circulating microRNAs (miRNAs) levels in patients with TRAPS, in comparison to controls without inflammatory diseases, and to correlate their levels with parameters of disease activity and/or disease severity. Expression levels of circulating miRNAs were measured by Agilent microarrays in 29 serum samples from 15 TRAPS patients carrying mutations known to be associated with high disease penetrance and from 8 controls without inflammatory diseases. Differentially expressed and clinically relevant miRNAs were detected using GeneSpring GX software. We identified a 6 miRNAs signature able to discriminate TRAPS from controls. Moreover, 4 miRNAs were differentially expressed between patients treated with the interleukin (IL)-1 receptor antagonist, anakinra, and untreated patients. Of these, miR-92a-3p and miR-150-3p expression was found to be significantly reduced in untreated patients, while their expression levels were similar to controls in samples obtained during anakinra treatment. MiR-92b levels were inversely correlated with the number of fever attacks/year during the 1st year from the index attack of TRAPS, while miR-377-5p levels were positively correlated with serum amyloid A (SAA) circulating levels. Our data suggest that serum miRNA levels show a baseline pattern in TRAPS, and may serve as potential markers of response to therapeutic intervention.

Working the endless puzzle of hereditary autoinflammatory disorders

Abstract Hereditary autoinflammatory disorders encompass manifold dysfunctions of innate immunity caused by mutations in genes coding for the main characters of the inflammatory scene: most of these conditions have an early onset, ranging from the first days of life to the first decades, and include hereditary periodic fevers, NLRP-related diseases, granulomatous and pyogenic syndromes, which are basically characterized by upturned inflammasome activity and overproduction of bioactive interleukin (IL)-1β and other proinflammatory cytokines. The discovery of a causative link between autoinflammation and IL-1β release has improved our understanding of the intimate mechanisms of innate immunity, and has likewise led to the identification of extraordinary treatments for many of these disorders.

Expanding spectrum of TNFRSF1A gene mutations among patients with idiopathic recurrent acute pericarditis

Although idiopathic recurrent acute pericarditis (IRAP) is generally presumed to derive from an autoimmune process, increasing interest is currently being devoted to autoinflammatory diseases, a group of disorders of the innate immune system caused by mutations of genes involved in the regulation or activation of the inflammatory response, without any apparent involvement of autoimmunity. The tumour necrosis factor receptor‐1‐associated periodic syndrome is the most common autosomal dominant autoinflammatory disorder and is caused by mutations in the TNFRSF1A gene encoding the 55‐kD receptor for tumour necrosis factor‐α. IRAP patients carrying TNFRSF1A gene mutations have been recently described. We report herein the first IRAP patients carrying the rare R104Q and D12E TNFRSF1A gene mutations, thus expanding the spectrum of tumour necrosis factor receptor‐1‐associated periodic syndrome mutations in IRAP patients.

OR10-004 - Circulating micrornas in TRAPS

To the best of our knowledge circulating miRNAs in TRAPS, as well as in other monogenic autoinflammatory disorders have never been investigated.

PReS-FINAL-1010: circulating micrornas in traps

To the best of our knowledge circulating miRNAs in TRAPS, as well as in other monogenic autoinflammatory disorders have never been investigated.

OP0074 First Report of Circulating Micrornas in Tumour Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS)

Background Tumor necrosis factor-receptor associated periodic syndrome (TRAPS) is the most common autosomal dominant autoinflammatory disorder. To the best of our knowledge circulating miRNAs in TRAPS, as well as in other monogenic autoinflammatory disorders have never been investigated. Objectives to evaluate circulating microRNAs (miRNAs) levels in patients with TRAPS, in comparison to healthy controls, and to correlate their levels to parameters of disease activity and/or disease severity Methods expression levels of circulating miRNAs were measured by Agilent microarrays in 29 serum samples from 15 TRAPS patients carrying mutations known to be associated with high disease penetrance and 8 healthy controls. Differentially expressed and clinically relevant miRNAs were detected using GeneSpring GX software Results we identified a 6 miRNAs signature able to discriminate TRAPS from healthy controls. Moreover, 4 miRNAs were differentially expressed between patients treated with the interleukyn (IL)-1 receptor antagonist anakinra and untreated patients. Of them, miR-92a-3p expression was found to be reduced in untreated patients, while its expression levels were similar to healthy controls in those samples from patients during anakinra treatment. MiR-92b levels were inversely correlated with the number of fever attacks/year during the 1st year from the index attack of TRAPS, while miR-377-5p levels were positively correlated with serum amyloid A (SAA) circulating levels. Conclusions serum miRNAs levels show a baseline pattern in TRAPS, and may serve as potential markers of response to therapeutic intervention Disclosure of Interest None Declared