title: Antigen-specific T-cell responses of leprosy patients.
abstract: The identification of human T-cell antigens of Mycobacterium leprae could improve treatment and help to disrupt the transmission of leprosy by directing diagnosis and vaccine programs. This study screened a panel of M. leprae recombinant proteins for T-cell recall responses, measured by gamma interferon (IFN-gamma) production, among leprosy patients. After initial studies using peripheral blood mononuclear cells from leprosy patients, we transitioned our studies to simple whole-blood assays (WBA), which are more applicable in field or clinical settings. T-cell responses generated in WBA using blood from individuals in Goiânia, Brazil, demonstrated that several M. leprae antigens (ML0276, ML0840, ML1623, ML2044, and 46f) elicited >0.5 IU/ml IFN-gamma, and these proteins were classified as immunogenic and leprosy specific. Several of these individual antigens were recognized by cells from >60% of Brazilian paucibacillary (PB) leprosy patients, and ML0276, ML0840, ML1623, and 46f complemented each other such that 82% of PB patients had strong (>1.25 IU/ml IFN-gamma) responses to at least one of these proteins. These proteins were also recognized by cells from a significant proportion of the household contacts of multibacillary leprosy patients, but in contrast, few responses were observed in active tuberculosis patients or healthy control groups from areas of endemicity. Our results indicate several potential candidate antigens which may be useful for either leprosy diagnosis or vaccination and demonstrate the utility of leprosy WBA that can be applied broadly in clinical or field settings.
authors.affiliation: Infectious Disease Research Institute, Seattle, WA 98104, USA. mduthie@idri.org
authors.forename: Malcolm S
authors.initials: MS
authors.lastname: Duthie
authors.forename: Wakako
authors.initials: W
authors.lastname: Goto
authors.forename: Greg C
authors.initials: GC
authors.lastname: Ireton
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Reece
authors.forename: Lucas H
authors.initials: LH
authors.lastname: Sampaio
authors.forename: A B
authors.initials: AB
authors.lastname: Grassi
authors.forename: Ana Lucia M
authors.initials: AL
authors.lastname: Sousa
authors.forename: Celina M T
authors.initials: CM
authors.lastname: Martelli
authors.forename: Mariane M A
authors.initials: MM
authors.lastname: Stefani
authors.forename: Steven G
authors.initials: SG
authors.lastname: Reed
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology; D001938:Brazil; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007918:Leprosy / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009166:Mycobacterium leprae / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D011994:Recombinant Proteins; D007371:Interferon-gamma
references.citation: Infect Immun. 2006 Jan;74(1):175-82
references.pmid: 16368971
references.citation: Infect Immun. 2003 Mar;71(3):1596-8
references.pmid: 12595485
references.citation: Lancet Infect Dis. 2004 Dec;4(12):761-76
references.pmid: 15567126
references.citation: J Clin Microbiol. 2003 May;41(5):1991-5
references.pmid: 12734239
references.citation: Nature. 2001 Feb 22;409(6823):1007-11
references.pmid: 11234002
references.citation: Indian J Lepr. 1998 Oct-Dec;70(4):369-88
references.pmid: 10189587
references.citation: J Immunol. 2005 Dec 15;175(12):7930-8
references.pmid: 16339528
references.citation: Int J Lepr Other Mycobact Dis. 1999 Jun;67(2):119-28
references.pmid: 10472363
references.citation: Scand J Immunol. 1999 Nov;50(5):541-9
references.pmid: 10564558
references.citation: Lepr Rev. 1994 Sep;65(3):175-80
references.pmid: 8942148
references.citation: Expert Rev Anti Infect Ther. 2005 Dec;3(6):981-93
references.pmid: 16307510
references.citation: Int J Lepr Other Mycobact Dis. 1999 Sep;67(3):279-86
references.pmid: 10575407
references.citation: Clin Microbiol Rev. 2006 Apr;19(2):338-81
references.pmid: 16614253
references.citation: Hum Immunol. 2006 Jun;67(6):439-45
references.pmid: 16728267
references.citation: Clin Exp Immunol. 2007 Nov;150(2):210-6
references.pmid: 17937676
references.citation: Int J Lepr Other Mycobact Dis. 2001 Mar;69(1):1-12
references.pmid: 11480310
references.citation: Lepr Rev. 2003 Sep;74(3):196-205
references.pmid: 14577464
references.citation: Clin Vaccine Immunol. 2007 Nov;14(11):1400-8
references.pmid: 17898185
references.citation: Infect Immun. 2005 Sep;73(9):5636-44
references.pmid: 16113281
references.citation: Lepr Rev. 2006 Mar;77(1):48-61
references.pmid: 16715690
references.citation: Expert Rev Mol Diagn. 2006 Sep;6(5):663-77
references.pmid: 17009902
references.citation: Lancet. 1992 Feb 22;339(8791):446-50
references.pmid: 1346818
references.citation: Clin Exp Immunol. 1999 May;116(2):263-9
references.pmid: 10337017
references.citation: Clin Vaccine Immunol. 2006 Mar;13(3):333-40
references.pmid: 16522774
references.citation: Clin Vaccine Immunol. 2008 Mar;15(3):522-33
references.pmid: 18199740
references.citation: FEMS Immunol Med Microbiol. 1999 Jul 15;24(4):405-9
references.pmid: 10435759
references.citation: Microbes Infect. 2006 Jul;8(8):2270-6
references.pmid: 16797206
references.citation: Int J Tuberc Lung Dis. 1998 Jun;2(6):441-2
references.pmid: 9626599
references.citation: Clin Exp Immunol. 1991 Apr;84(1):103-8
references.pmid: 2015700