02412nas a2200253   4500000000100000008004100001100001600042700002100058700001300079700001400092700001500106700001400121700002700135700001500162700001800177700001200195700001500207245013900222856007100361300000900432490000600441520169700447022001402144       2018                            d1 aBarbosa MGM1 aAndrade Silva BJ1 aAssis TQ1 aPrata RBS1 aFerreira H1 aAndrade P1 aPaixão de Oliveira JA1 ada Silva G1 aCosta Nery JA1 aSarno E1 aPinheiro R00aAutophagy impairment is associated with increased inflammasome activation and reversal reaction development in multibacillary leprosy.  uhttps://www.frontiersin.org/articles/10.3389/fimmu.2018.01223/full  a12230 v93 a<p>Leprosy reactions are responsible for incapacities in leprosy and represent the major cause of permanent neuropathy. The identification of biomarkers able to identify patients more prone to develop reaction could contribute to adequate clinical management and the prevention of disability. Reversal reaction may occur in unstable borderline patients and also in lepromatous patients. To identify biomarker signature profiles related with the reversal reaction onset, multibacillary patients were recruited and classified accordingly the occurrence or not of reversal reaction during or after multidrugtherapy. Analysis of skin lesion cells at diagnosis of multibacillary leprosy demonstrated that in the group that developed reaction (T1R) in the future there was a downregulation of autophagy associated with the overexpression of and . The autophagy impairment in T1R group was associated with increased expression of , caspase-1 (p10) and IL-1β production. In addition, analysis of IL-1β production in serum from multibacillary patients demonstrated that patients who developed reversal reaction have significantly increased concentrations of IL-1β at diagnosis, suggesting that the pattern of innate immune responses could predict the reactional episode outcome. analysis demonstrated that the blockade of autophagy with 3-methyladenine (3-MA) in -stimulated human primary monocytes increased the assembly of NLRP3 specks assembly, and it was associated with an increase of IL-1β and IL-6 production. Together, our data suggest an important role for autophagy in multibacillary leprosy patients to avoid exacerbated inflammasome activation and the onset of reversal reaction.</p>
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