title: ML0405 and ML2331 are antigens of Mycobacterium leprae with potential for diagnosis of leprosy.
abstract: Despite the success of multidrug therapy in reducing the number of registered leprosy cases worldwide, evidence suggests that Mycobacterium leprae continues to be transmitted. A serological diagnostic test capable of identifying and allowing treatment of early-stage disease could reduce transmission and prevent the onset of the disability, a common complication of the disease in later stages. Serological diagnosis based on antibody recognition of phenolic glycolipid I (PGL-I) cannot reliably identify individuals with lower bacterial indices (BI). One strategy that might improve this situation is the provision of highly specific serological antigens that may be combined with PGL-I to improve the sensitivity of diagnosis. Using serological expression cloning with a serum pool of untreated lepromatous leprosy (LL) patients, we identified 14 strongly reactive M. leprae proteins, 5 of which were previously unstudied. We present results suggesting that two of these proteins, ML0405 and ML2331, demonstrate the ability to specifically identify LL/borderline lepromatous (BL) patients on the basis of immunoglobulin G (IgG) reactivity. In a household contact study, LL index cases were identified on the basis of this reactivity, while household contacts of these patients demonstrated undetectable reactivity. At a serum dilution of 1:800, suitable to reduce background PGL-I IgM reactivity, two BL patients with a BI of <4 showed anti-human polyvalent immunoglobulin G, A, and M reactivity measured with a combination of ML0405, ML2331, and natural disaccharide O-linked human serum albumin (NDOHSA) (synthetic PGL-I) that was markedly higher than IgM reactivity to NDOHSA alone. We suggest that ML0405 and ML2331 may have utility in serological leprosy diagnosis.
authors.affiliation: IDRI, 1124 Columbia Street, Suite 400, Seattle, WA 98104, USA. sreed@idri.org
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Reece
authors.forename: Greg
authors.initials: G
authors.lastname: Ireton
authors.forename: Raodoh
authors.initials: R
authors.lastname: Mohamath
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Guderian
authors.forename: Wakako
authors.initials: W
authors.lastname: Goto
authors.forename: Robert
authors.initials: R
authors.lastname: Gelber
authors.forename: Nathan
authors.initials: N
authors.lastname: Groathouse
authors.forename: John
authors.initials: J
authors.lastname: Spencer
authors.forename: Patrick
authors.initials: P
authors.lastname: Brennan
authors.forename: Steven G
authors.initials: SG
authors.lastname: Reed
mesh_terms: D000907:Antibodies, Bacterial / Q000378:metabolism; D000937:Antigen-Antibody Reactions; D000942:Antigens, Bacterial / Q000097:blood* / Q000276:immunology; D001426:Bacterial Proteins / Q000097:blood* / Q000276:immunology; D006017:Glycolipids; D006801:Humans; D007918:Leprosy / Q000175:diagnosis* / Q000276:immunology; D015440:Leprosy, Lepromatous / Q000276:immunology; D015441:Leprosy, Tuberculoid / Q000276:immunology; D009166:Mycobacterium leprae / Q000276:immunology*; D020539:Sequence Analysis, Protein
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D006017:Glycolipids; C045169:phenolic glycolipid I, Mycobacterium leprae