03319nas a2200385 4500000000100000008004100001260005100042653001000093653000900103653004200112653001500154653003100169653003100200653001100231653001900242653001100261653004800272653001200320653000900332653001600341653001600357100002200373700001200395700001800407700002300425700001600448700001200464700001500476245015200491856007900643300001100722490000600733520218000739022001402919 2011 d c2011bPublic Library of ScienceaSan Francisco10aAdult10aAged10aAntiretroviral Therapy, Highly Active10aBiomarkers10aCD4-Positive T-Lymphocytes10aCD8-Positive T-Lymphocytes10aFemale10aHIV Infections10aHumans10aImmune Reconstitution Inflammatory Syndrome10aleprosy10aMale10aMiddle Aged10aYoung Adult1 aGiacoia-Gripp CBW1 aSales A1 aCosta Nery JA1 aSantos-Oliveira JR1 aOliveira AL1 aSarno E1 aMorgado MG00aEvaluation of cellular phenotypes implicated in immunopathogenesis and monitoring immune reconstitution inflammatory syndrome in HIV/leprosy cases. uhttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0028735 ae287350 v63 a

BACKGROUND: It is now evident that HAART-associated immunological improvement often leads to a variety of new clinical manifestations, collectively termed immune reconstitution inflammatory syndrome, or IRIS. This phenomenon has already been described in cases of HIV coinfection with Mycobacterium leprae, most of them belonging to the tuberculoid spectrum of leprosy disease, as observed in leprosy reversal reaction (RR). However, the events related to the pathogenesis of this association need to be clarified. This study investigated the immunological profile of HIV/leprosy patients, with special attention to the cellular activation status, to better understand the mechanisms related to IRIS/RR immunopathogenesis, identifying any potential biomarkers for IRIS/RR intercurrence.

METHODS/PRINCIPAL FINDINGS: Eighty-five individuals were assessed in this study: HIV/leprosy and HIV-monoinfected patients, grouped according to HIV-viral load levels, leprosy patients without HIV coinfection, and healthy controls. Phenotypes were evaluated by flow cytometry for T cell subsets and immune differentiation/activation markers. As expected, absolute counts of the CD4+ and CD8+ T cells from the HIV-infected individuals changed in relation to those of the leprosy patients and controls. However, there were no significant differences among the groups, whether in the expression of cellular differentiation phenotypes or cellular activation, as reflected by the expression of CD38 and HLA-DR. Six HIV/leprosy patients identified as IRIS/RR were analyzed during IRIS/RR episodes and after prednisone treatment. These patients presented high cellular activation levels regarding the expression of CD38 in CD8+ cells T during IRIS/RR (median: 77,15%), dropping significantly (p<0,05) during post-IRIS/RR moments (median: 29,7%). Furthermore, an increase of cellular activation seems to occur prior to IRIS/RR.

CONCLUSION/SIGNIFICANCE: These data suggest CD38 expression in CD8+ T cells interesting tool identifying HIV/leprosy individuals at risk for IRIS/RR. So, a comparative investigation to leprosy patients at RR should be conducted.

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