03323nas a2200565   4500000000100000008004100001260006500042653001000107653000900117653002400126653001500150653001500165653001100180653001400191653001300205653001100218653001100229653002100240653001200261653000900273653001600282653002500298653002200323653001400345653001400359653001600373100001200389700001400401700002300415700001500438700001100453700001400464700001000478700001400488700001000502700001300512700001500525700001700540700001300557700001900570700001500589700001500604700001600619245010100635856007600736300001200812490000800824520191100832022001402743       2012                            d  c2012 May 15bAmerican Association of ImmunologistsaBethesda10aAdult10aAged10aAntigens, Bacterial10aBangladesh10aBiomarkers10aBrazil10aCytokines10aEthiopia10aFemale10aHumans10aInterferon-gamma10aleprosy10aMale10aMiddle Aged10aMycobacterium leprae10aRepublic of Korea10aTh1 Cells10aTh2 Cells10aYoung Adult1 aGeluk A1 aBobosha K1 aPloeg-van Schip JJ1 aSpencer JS1 aBanu S1 aMartins M1 aCho S1 aFranken K1 aKim H1 aBekele Y1 aUddin MK M1 aAbdul Hadi S1 aAseffa A1 aPessolani MC V1 aPereira GM1 aDockrell H1 aOttenhoff T00aNew biomarkers with relevance to leprosy diagnosis applicable in areas hyperendemic for leprosy.  uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3345093/pdf/nihms364583.pdf  a4782-910 v1883 a<p>Leprosy is not eradicable with currently available diagnostics or interventions, as evidenced by its stable incidence. Early diagnosis of Mycobacterium leprae infection should therefore be emphasized in leprosy research. It remains challenging to develop tests based on immunological biomarkers that distinguish individuals controlling bacterial replication from those developing disease. To identify biomarkers for field-applicable diagnostics, we determined cytokines/chemokines induced by M. leprae proteins in blood of leprosy patients and endemic controls (EC) from high leprosy-prevalence areas (Bangladesh, Brazil, Ethiopia) and from South Korea, where leprosy is not endemic anymore. M. leprae-sonicate-induced IFN-γ was similar for all groups, excluding M. leprae/IFN-γ as a diagnostic readout. By contrast, ML2478 and ML0840 induced high IFN-γ concentrations in Bangladeshi EC, which were completely absent for South Korean controls. Importantly, ML2478/IFN-γ could indicate distinct degrees of M. leprae exposure, and thereby the risk of infection and transmission, in different parts of Brazilian and Ethiopian cities. Notwithstanding these discriminatory responses, M. leprae proteins did not distinguish patients from EC in one leprosy-endemic area based on IFN-γ. Analyses of additional cytokines/chemokines showed that M. leprae and ML2478 induced significantly higher concentrations of MCP-1, MIP-1β, and IL-1β in patients compared with EC, whereas IFN-inducible protein-10, like IFN-γ, differed between EC from areas with dissimilar leprosy prevalence. This study identifies M. leprae-unique Ags, particularly ML2478, as biomarker tools to measure M. leprae exposure using IFN-γ or IFN-inducible protein-10, and also shows that MCP-1, MIP-1β, and IL-1β can potentially distinguish pathogenic immune responses from those induced during asymptomatic exposure to M. leprae.</p>  a1550-6606