02916nas a2200325   4500000000100000008004100001100001400042700001400056700001600070700001300086700001600099700001400115700001700129700001500146700001400161700001800175700001600193700001500209700001800224700001400242700001200256700001500268700001200283245011800295856008000413300001300493490000700506520206300513022001402576       2016                            d1 aSchmitz V1 aPrata RBS1 aBarbosa MGM1 aMendes M1 aBrandão SS1 aAmadeu TP1 aRodrigues LS1 aFerreira H1 aCosta FMR1 aDos Santos JB1 aPacheco FDS1 aMachado AM1 aCosta Nery JA1 aHacker MA1 aSales A1 aPinheiro R1 aSarno E00aExpression of CD64 on Circulating Neutrophils Favoring Systemic Inflammatory Status in Erythema Nodosum Leprosum.  uhttp://journals.plos.org/plosntds/article?id=10.1371%2Fjournal.pntd.0004955  ae00049550 v103 a<p>Erythema Nodosum Leprosum (ENL) is an immune reaction in leprosy that aggravates the patient´s clinical condition. ENL presents systemic symptoms of an acute infectious syndrome with high leukocytosis and intense malaise clinically similar to sepsis. The treatment of ENL patients requires immunosuppression and thus needs to be early and efficient to prevent both disabilities and permanent nerve damage. Some patients experience multiple episodes of ENL and prolonged use of immunosuppressive drugs may lead to serious adverse effects. Thalidomide treatment is extremely effective at ameliorating ENL symptoms. Several mechanisms have been proposed to explain the efficacy of thalidomide in ENL, including the inhibition of TNF production. Given its teratogenicity, thalidomide is prohibitive for women of childbearing age. A rational search for molecular targets during ENL episodes is essential to better understand the disease mechanisms involved, which may also lead to the discovery of new drugs and diagnostic tests. Previous studies have demonstrated that IFN-γ and GM-CSF, involved in the induction of CD64 expression, increase during ENL. The aim of the present study was to investigate CD64 expression during ENL and whether thalidomide treatment modulated its expression. Leprosy patients were allocated to one of five groups: (1) Lepromatous leprosy, (2) Borderline leprosy, (3) Reversal reaction, (4) ENL, and (5) ENL 7 days after thalidomide treatment. The present study demonstrated that CD64 mRNA and protein were expressed in ENL lesions and that thalidomide treatment reduced CD64 expression and neutrophil infiltrates-a hallmark of ENL. We also showed that ENL blood neutrophils exclusively expressed CD64 on the cell surface and that thalidomide diminished overall expression. Patient classification based on clinical symptoms found that severe ENL presented high levels of neutrophil CD64. Collectively, these data revealed that ENL neutrophils express CD64, presumably contributing to the immunopathogenesis of the disease.</p>
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