03066nas a2200529 4500000000100000008004100001260001600042653002400058653003100082653003100113653002500144653002000169653004100189653002200230653001100252653002100263653001200284653002800296653002500324100001500349700001500364700001000379700001700389700001600406700001400422700001400436700001600450700001200466700001500478700001200493700001400505700001500519700001600534700001200550700001000562700001300572700001100585700001500596700001900611245012600630856006200756300001100818490000800829050001600837520166900853022001402522 2005 d c2005 Dec 1510aAntigens, Bacterial10aCD4-Positive T-Lymphocytes10aCD8-Positive T-Lymphocytes10aCase-Control Studies10aCells, Cultured10aDiagnostic Techniques and Procedures10aGenome, Bacterial10aHumans10aInterferon-gamma10aleprosy10aLeukocytes, Mononuclear10aMycobacterium leprae1 aSpencer JS1 aDockrell H1 aKim H1 aMarques MA M1 aWilliams DL1 aMartins M1 aMartins M1 aLima MC B S1 aSarno E1 aPereira GM1 aMatos H1 aFonseca L1 aSampaio EP1 aOttenhoff T1 aGeluk A1 aCho S1 aStoker N1 aCole S1 aBrennan PJ1 aPessolani MC V00aIdentification of specific proteins and peptides in Mycobacterium leprae suitable for the selective diagnosis of leprosy. uhttp://www.jimmunol.org/content/175/12/7930.full.pdf+html a7930-80 v175 aSPENCER20053 a

Diagnosis of leprosy is a major obstacle to disease control and has been compromised in the past due to the lack of specific reagents. We have used comparative genome analysis to identify genes that are specific to Mycobacterium leprae and tested both recombinant proteins and synthetic peptides from a subset of these for immunological reactivity. Four unique recombinant proteins (ML0008, ML0126, ML1057, and ML2567) and a panel of 58 peptides (15 and 9 mer) were tested for IFN-gamma responses in PBMC from leprosy patients and contacts, tuberculosis patients, and endemic and nonendemic controls. The responses to the four recombinant proteins gave higher levels of IFN-gamma production, but less specificity, than the peptides. Thirty-five peptides showed IFN-gamma responses only in the paucibacillary leprosy and household contact groups, with no responses in the tuberculosis or endemic control groups. High frequencies of IFN-gamma-producing CD4+ and CD8+ T cells specific for the 15- and 9-mer peptides were observed in the blood of a paucibacillary leprosy patient. 9-mer peptides preferentially activated CD8+ T cells, while the 15-mer peptides were efficient in inducing responses in both the CD4+ and CD8+ T cell subsets. Four of the six 9-mer peptides tested showed promising specificity, indicating that CD8+ T cell epitopes may also have diagnostic potential. Those peptides that provide specific responses in leprosy patients from an endemic setting could potentially be developed into a rapid diagnostic test for the early detection of M. leprae infection and epidemiological surveys of the incidence of leprosy, of which little is known.

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