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Ciccia F.,University of Palermo | Rizzo A.,Cervello | Triolo G.,University of Palermo
Current Opinion in Rheumatology

Purpose of review Subclinical gut inflammation has been described in a significant proportion of patients with ankylosing spondylitis (AS), up to 10% of them developing it during the time of clinically overt inflammatory bowel disease. Histologic, immunologic, and intestinal microbiota alterations characterize the AS gut. Recent findings Microbial dysbiosis as well as alterations of innate immune responses have been demonstrated in the gut of AS. Furthermore, a growing body of evidence suggests that the gut of AS patients may be actively involved in the pathogenesis of AS through the production of proinflammatory cytokines, such as IL-23p19, and the differentiation of potentially pathogenic innate lymphoid cells producing IL-22 and IL-17. Finally, a strong correlation between the presence of subclinical gut inflammation and the degree of spine inflammation have been also proved in AS. Summary Subclinical gut inflammation and innate immune responses in AS may be considered a possible consequence of microbial dysbiosis. Relationships between cause and effect remain, however, to be answered. © Copyright 2015 Wolters Kluwer Health, Inc. All rights reserved. Source

Fries W.,Messina University | Cottone M.,Cervello | Cascio A.,Messina University
Alimentary Pharmacology and Therapeutics

Background Recently, there have been increasingly frequent reports on the occurrence of macrophage activation syndrome (MAS) in patients with inflammatory bowel disease (IBD). Clinically, MAS is characterized mainly by fever, hepatosplenomegaly, cytopenia, and elevated circulating ferritin and CD25. Mortality, even if diagnosed rapidly, is high. Aim To identify all reports on MAS in IBD and to establish data on triggering agents, immunosuppression leading to MAS, and mortality. Methods A language unrestricted search on Pubmed and Scopus relating to the past 30 years was carried out by matching the following search-terms: h(a)emophagocytic lymphohistiocytosis OR h(a)emophagocytic lymphohistiocytic syndrome OR macrophage activation syndrome OR opportunistic infections OR cytomegalovirus OR Epstein-Barr virus AND Crohn's disease OR ulcerative colitis OR inflammatory bowel disease(s). Results Fifty cases were identified with an overall mortality of 30%. Virus-related MAS associated with cytomegalovirus or Epstein-Barr virus infections represents the main type of MAS, but in isolated cases bacterial infections precipitated the syndrome. In four cases (8%), a lymphoma was present at the time of MAS diagnosis or developed shortly thereafter. Thiopurine monotherapy was given before MAS onset in 56% of the patients, whereas multiple immunosuppression, including biologics, was administered to 24%. Conclusions In IBD patients, the syndrome appears to be triggered by infections, but genetic susceptibility may contribute to its development. Since immunosuppressive therapy represents the backbone of therapeutic interventions in IBD, with the risk of new, or the reactivation of latent infections, even more frequent cases of macrophage activation syndrome may be expected. © 2013 Blackwell Publishing Ltd. Source

Lanzuolo C.,Dulbecco Telethon Institute | Lanzuolo C.,CNR Institute of Neurobiology and Molecular Medicine | Sardo F.L.,Dulbecco Telethon Institute | Diamantini A.,Cervello | Orlando V.,Dulbecco Telethon Institute
PLoS Genetics

Polycomb group (PcG) proteins are part of a conserved cell memory system that conveys epigenetic inheritance of silenced transcriptional states through cell division. Despite the considerable amount of information about PcG mechanisms controlling gene silencing, how PcG proteins maintain repressive chromatin during epigenome duplication is still unclear. Here we identified a specific time window, the early S phase, in which PcG proteins are recruited at BX-C PRE target sites in concomitance with H3K27me3 repressive mark deposition. Notably, these events precede and are uncoupled from PRE replication timing, which occurs in late S phase when most epigenetic signatures are reduced. These findings shed light on one of the key mechanisms for PcG-mediated epigenetic inheritance during S phase, suggesting a conserved model in which the PcG-dependent H3K27me3 mark is inherited by dilution and not by de novo methylation occurring at the time of replication. © 2011 Lanzuolo et al. Source

Fiorino G.,center | Girolomoni G.,University of Verona | Lapadula G.,University of Bari | Orlando A.,Cervello | And 2 more authors.
Autoimmunity Reviews

Biological agents are widely used in rheumatology, dermatology and inflammatory bowel disease. Evidence about their efficacy and safety has been strengthened for all those therapeutic indications over the last decade. Biosimilar agents are monoclonal antibodies similar to previously approved biologics. In the European Union, they have been approved for all the indications in the management of immune-mediated inflammatory diseases (IMIDs), although data only in rheumatoid arthritis and ankylosing spondylitis are currently available. Direct evidence on efficacy, safety, and immunogenicity of biosimilars is mandatory in psoriasis, psoriatic arthritis, and inflammatory bowel disease, as well as in children. Based on the current evidence in the literature, we present the joint official position of the Italian Societies of Rheumatology, Dermatology and Inflammatory Bowel Disease on the use of biosimilars in IMIDs. © 2014 Elsevier B.V. Source

Mancuso L.,Cervello | Mancuso A.,Epatologia e Gastroenterologia
World Journal of Gastroenterology

Portopulmonary hypertension (PPHTN) is a known complication of cirrhosis. Moderate-to-severe PPHTN implies an extremely poor prognosis. It occurs in 5%-10% of patients referred for liver transplantation (LT), and probably with an higher incidence in patients with large portosystemic shunts. Patients with moderate-tosevere pulmonary hypertension have been previously excluded from LT because of the extremely high surgical risk and since the post-transplant outcome reported was poor. Recently, new perspectives in the management of patients with portopulmonary hypertension are emerging. In fact, some pulmonary vasoactive drugs have become routine in the treatment of patients with idiopathic pulmonary hypertension. These drugs, particularly epoprostenol, have been recently introduced in the treatment of patients with PPHTN, and have been shown to be effective in reducing pulmonary artery pressure as well as pulmonary vascular resistances. Furthermore, recent studies seem to demonstrate that treatment with pulmonary vasoactive drugs could allow liver transplantation with acceptable surgical risks and excellent survival. Although there are not large series nor prospective studies addressing this topic, the clinical scenario of patients with PPHTN seems to be positively changing. © 2013 Baishideng Publishing Group Co., Limited. All rights reserved. Source

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