{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T18:37:24Z","timestamp":1778870244826,"version":"3.51.4"},"reference-count":35,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2006,3,1]],"date-time":"2006-03-01T00:00:00Z","timestamp":1141171200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Clin Vaccine Immunol"],"published-print":{"date-parts":[[2006,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Despite the success of multidrug therapy in reducing the number of registered leprosy cases worldwide, evidence suggests that<jats:italic>Mycobacterium leprae<\/jats:italic>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<jats:italic>M. leprae<\/jats:italic>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 &lt;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.<\/jats:p>","DOI":"10.1128\/cvi.13.3.333-340.2006","type":"journal-article","created":{"date-parts":[[2006,3,7]],"date-time":"2006-03-07T18:48:00Z","timestamp":1141757280000},"page":"333-340","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":46,"title":["ML0405 and ML2331 Are Antigens of<i>Mycobacterium leprae<\/i>with Potential for Diagnosis of Leprosy"],"prefix":"10.1128","volume":"13","author":[{"given":"Stephen T.","family":"Reece","sequence":"first","affiliation":[{"name":"Infectious Disease Research Institute, Seattle, Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Greg","family":"Ireton","sequence":"additional","affiliation":[{"name":"Infectious Disease Research Institute, Seattle, Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raodoh","family":"Mohamath","sequence":"additional","affiliation":[{"name":"Infectious Disease Research Institute, Seattle, Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Guderian","sequence":"additional","affiliation":[{"name":"Infectious Disease Research Institute, Seattle, Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wakako","family":"Goto","sequence":"additional","affiliation":[{"name":"Infectious Disease Research Institute, Seattle, Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Gelber","sequence":"additional","affiliation":[{"name":"Leonard Wood Memorial Center for Leprosy Research, Cebu City, Philippines"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathan","family":"Groathouse","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Colorado State University, Fort Collins, Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Spencer","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Colorado State University, Fort Collins, Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Brennan","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Colorado State University, Fort Collins, Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven G.","family":"Reed","sequence":"additional","affiliation":[{"name":"Infectious Disease Research Institute, Seattle, Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1016\/S0140-6736(04)15952-7","volume":"363","year":"2004","unstructured":"Britton, W. J., and D. N. Lockwood. 2004. Leprosy. Lancet363:1209-1219.","journal-title":"Lancet"},{"key":"e_1_3_2_3_2","first-page":"533","volume":"61","year":"1993","unstructured":"Chanteau, S., P. Glaziou, C. Plichart, P. Luquiaud, R. Plichart, J. F. Faucher, and J. L. Cartel. 1993. Low predictive value of PGL-I serology for the early diagnosis of leprosy in family contacts: results of a 10-year prospective field study in French Polynesia. Int. J. Lepr. Other Mycobact. Dis.61:533-541.","journal-title":"Int. J. Lepr. Other Mycobact. Dis."},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"4370","DOI":"10.4049\/jimmunol.141.12.4370","volume":"141","year":"1988","unstructured":"Cherayil, B. J., and R. A. Young. 1988. A 28-kDa protein from Mycobacterium leprae is a target of the human antibody response in lepromatous leprosy. J. Immunol.141:4370-4375.","journal-title":"J. Immunol."},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/CDLI.8.1.138-142.2001"},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1093\/infdis\/150.3.311","volume":"150","year":"1984","unstructured":"Cho, S. N., T. Fujiwara, S. W. Hunter, T. H. Rea, R. H. Gelber, and P. J. Brennan. 1984. Use of an artificial antigen containing the 3,6-di-O-methyl-beta-D-glucopyranosyl epitope for the serodiagnosis of leprosy. J. Infect. Dis.150:311-322.","journal-title":"J. Infect. Dis."},{"key":"e_1_3_2_7_2","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1128\/CDLI.11.5.897-900.2004","volume":"11","year":"2004","unstructured":"Douglas, J. T., R. V. Cellona, T. T. Fajardo, Jr., R. M. Abalos, M. V. Balagon, and P. R. Klatser. 2004. Prospective study of serological conversion as a risk factor for development of leprosy among household contacts. Clin. Diagn. Lab. Immunol.11:897-900.","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"e_1_3_2_8_2","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1093\/oxfordjournals.aje.a009195","volume":"146","year":"1997","unstructured":"Fine, P. E., J. A. Sterne, J. M. Ponnighaus, L. Bliss, J. Saui, A. Chihana, M. Munthali, and D. K. Warndorff. 1997. Household and dwelling contact as risk factors for leprosy in northern Malawi. Am. J. Epidemiol.146:91-102.","journal-title":"Am. J. Epidemiol."},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"10676","DOI":"10.1073\/pnas.0504922102","volume":"102","year":"2005","unstructured":"Fortune, S. M., A. Jaeger, D. A. Sarracino, M. R. Chase, C. M. Sassetti, D. R. Sherman, B. R. Bloom, and E. J. Rubin. 2005. Mutually dependent secretion of proteins required for mycobacterial virulence. Proc. Natl. Acad. Sci. USA102:10676-10681.","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"e_1_3_2_10_2","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1093\/bioinformatics\/bti057","volume":"21","year":"2005","unstructured":"Gardy, J. L., M. R. Laird, F. Chen, S. Rey, C. J. Walsh, M. Ester, and F. S. Brinkman. 2005. PSORTb v. 2.0: expanded prediction of bacterial protein subcellular localization and insights gained from comparative proteome analysis. Bioinformatics21:617-623.","journal-title":"Bioinformatics"},{"key":"e_1_3_2_11_2","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/0035-9203(95)90018-7","volume":"89","year":"1995","unstructured":"Hatta, M., S. M. van Beers, B. Madjid, A. Djumadi, M. Y. de Wit, and P. R. Klatser. 1995. Distribution and persistence of Mycobacterium leprae nasal carriage among a population in which leprosy is endemic in Indonesia. Trans. R. Soc. Trop. Med. Hyg.89:381-385.","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.41.2.723-729.2003"},{"key":"e_1_3_2_13_2","first-page":"883","volume":"9","year":"2002","unstructured":"Houghton, R. L., M. J. Lodes, D. C. Dillon, L. D. Reynolds, C. H. Day, P. D. McNeill, R. C. Hendrickson, Y. A. Skeiky, D. P. Sampaio, R. Badaro, K. P. Lyashchenko, and S. G. Reed. 2002. Use of multiepitope polyproteins in serodiagnosis of active tuberculosis. Clin. Diagn. Lab. Immunol.9:883-891.","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"e_1_3_2_14_2","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1073\/pnas.84.6.1679","volume":"84","year":"1987","unstructured":"Husson, R. N., and R. A. Young. 1987. Genes for the major protein antigens of Mycobacterium tuberculosis: the etiologic agents of tuberculosis and leprosy share an immunodominant antigen. Proc. Natl. Acad. Sci. USA84:1679-1683.","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"e_1_3_2_15_2","first-page":"S67","volume":"71","year":"2000","unstructured":"Klatser, P. R. 2000. Use of a Mycobacterium leprae dipstick to classify patients with leprosy. Lepr. Rev.71:S67-S72.","journal-title":"Lepr. Rev."},{"key":"e_1_3_2_16_2","first-page":"185","volume":"58","year":"1986","unstructured":"Kumar, S., K. D. Moudgil, A. H. Band, P. R. Naraynan, S. K. Gupta, A. K. Sharma, and G. P. Talwar. 1986. A dot enzyme immunoassay for detection of IgM antibodies against phenolic glycolipid-I in sera from leprosy patients. Indian J. Lepr.58:185-190.","journal-title":"Indian J. Lepr."},{"key":"e_1_3_2_17_2","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1073\/pnas.88.3.1054","volume":"88","year":"1991","unstructured":"Laal, S., Y. D. Sharma, H. K. Prasad, A. Murtaza, S. Singh, S. Tangri, R. S. Misra, and I. Nath. 1991. Recombinant fusion protein identified by lepromatous sera mimics native Mycobacterium leprae in T-cell responses across the leprosy spectrum. Proc. Natl. Acad. Sci. USA88:1054-1058.","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"e_1_3_2_18_2","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1111\/j.1365-3083.1993.tb01709.x","volume":"38","year":"1993","unstructured":"Launois, P., M. N. Niang, J. L. Sarthou, F. Rivier, A. Drowart, J. P. Van Vooren, J. Millan, and K. Huygen. 1993. T-cell stimulation with purified mycobacterial antigens in patients and healthy subjects infected with Mycobacterium leprae: secreted antigen 85 is another immunodominant antigen. Scand. J. Immunol.38:167-176.","journal-title":"Scand. J. Immunol."},{"key":"e_1_3_2_19_2","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1136\/bmj.324.7352.1516","volume":"324","year":"2002","unstructured":"Lockwood, D. N. 2002. Leprosy elimination\u2014a virtual phenomenon or a reality? BMJ324:1516-1518.","journal-title":"BMJ"},{"key":"e_1_3_2_20_2","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1172\/JCI200420295","volume":"113","year":"2004","unstructured":"Lodes, M. J., Y. Cong, C. O. Elson, R. Mohamath, C. J. Landers, S. R. Targan, M. Fort, and R. M. Hershberg. 2004. Bacterial flagellin is a dominant antigen in Crohn disease. J. Clin. Investig.113:1296-1306.","journal-title":"J. Clin. Investig."},{"key":"e_1_3_2_21_2","first-page":"91","volume":"94","year":"2004","unstructured":"Lodes, M. J., D. C. Dillon, R. L. Houghton, and Y. A. Skeiky. 2004. Expression cloning. Methods Mol. Med.94:91-106.","journal-title":"Methods Mol. Med."},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.39.7.2485-2493.2001"},{"key":"e_1_3_2_23_2","doi-asserted-by":"crossref","first-page":"312","DOI":"10.4049\/jimmunol.147.1.312","volume":"147","year":"1991","unstructured":"McKenzie, K. R., E. Adams, W. J. Britton, R. J. Garsia, and A. Basten. 1991. Sequence and immunogenicity of the 70-kDa heat shock protein of Mycobacterium leprae. J. Immunol.147:312-319.","journal-title":"J. Immunol."},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.12.5595-5602.1994"},{"key":"e_1_3_2_25_2","first-page":"208","volume":"66","year":"1998","unstructured":"Naito, M., S. Izumi, and T. Yamada. 1998. Two-dimensional electrophoretic analysis of humoral responses to culture filtrate of Mycobacterium bovis BCG in patients with leprosy and tuberculosis. Int. J. Lepr. Other Mycobact. Dis.66:208-213.","journal-title":"Int. J. Lepr. Other Mycobact. Dis."},{"key":"e_1_3_2_26_2","first-page":"196","volume":"74","year":"2003","unstructured":"Oskam, L., E. Slim, and S. Buhrer-Sekula. 2003. Serology: recent developments, strengths, limitations and prospects: a state of the art overview. Lepr. Rev.74:196-205.","journal-title":"Lepr. Rev."},{"key":"e_1_3_2_27_2","first-page":"301","volume":"68","year":"1997","unstructured":"Ramaprasad, P., A. Fernando, S. Madhale, J. R. Rao, V. K. Edward, P. D. Samson, P. R. Klatser, M. Y. de Wit, W. C. Smith, and I. A. Cree. 1997. Transmission and protection in leprosy: indications of the role of mucosal immunity. Lepr. Rev.68:301-315.","journal-title":"Lepr. Rev."},{"key":"e_1_3_2_28_2","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/S0968-0004(03)00062-8","volume":"28","year":"2003","unstructured":"Rigden, D. J., M. J. Jedrzejas, and M. Y. Galperin. 2003. Amidase domains from bacterial and phage autolysins define a family of gamma-D,L-glutamate-specific amidohydrolases. Trends Biochem. Sci.28:230-234.","journal-title":"Trends Biochem. Sci."},{"key":"e_1_3_2_29_2","first-page":"279","volume":"67","year":"1999","unstructured":"Roche, P. W., S. S. Failbus, W. J. Britton, and R. Cole. 1999. Rapid method for diagnosis of leprosy by measurements of antibodies to the M. leprae 35-kDa protein: comparison with PGL-I antibodies detected by ELISA and \u201cdipstick\u201d methods. Int. J. Lepr. Other Mycobact. Dis.67:279-286.","journal-title":"Int. J. Lepr. Other Mycobact. Dis."},{"key":"e_1_3_2_30_2","doi-asserted-by":"crossref","first-page":"12989","DOI":"10.1073\/pnas.2134250100","volume":"100","year":"2003","unstructured":"Sassetti, C. M., and E. J. Rubin. 2003. Genetic requirements for mycobacterial survival during infection. Proc. Natl. Acad. Sci. USA100:12989-12994.","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"e_1_3_2_31_2","doi-asserted-by":"crossref","first-page":"9857","DOI":"10.1073\/pnas.96.17.9857","volume":"96","year":"1999","unstructured":"Shimoji, Y., V. Ng, K. Matsumura, V. A. Fischetti, and A. Rambukkana. 1999. A 21-kDa surface protein of Mycobacterium leprae binds peripheral nerve laminin-2 and mediates Schwann cell invasion. Proc. Natl. Acad. Sci. USA96:9857-9862.","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.6.3161-3170.2004"},{"key":"e_1_3_2_33_2","first-page":"119","volume":"67","year":"1999","unstructured":"van Beers, S. M., M. Hatta, and P. R. Klatser. 1999. Patient contact is the major determinant in incident leprosy: implications for future control. Int. J. Lepr. Other Mycobact. Dis.67:119-128.","journal-title":"Int. J. Lepr. Other Mycobact. Dis."},{"key":"e_1_3_2_34_2","first-page":"1","volume":"77","year":"2002","unstructured":"World Health Organization. 2002. Leprosy. Global situation. Wkly. Epidemiol. Rec.77:1-8.","journal-title":"Wkly. Epidemiol. Rec."},{"key":"e_1_3_2_35_2","doi-asserted-by":"crossref","first-page":"4267","DOI":"10.1073\/pnas.85.12.4267","volume":"85","year":"1988","unstructured":"Young, D., R. Lathigra, R. Hendrix, D. Sweetser, and R. A. Young. 1988. Stress proteins are immune targets in leprosy and tuberculosis. Proc. Natl. Acad. Sci. USA85:4267-4270.","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"e_1_3_2_36_2","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/316450a0","volume":"316","year":"1985","unstructured":"Young, R. A., V. Mehra, D. Sweetser, T. Buchanan, J. Clark-Curtiss, R. W. Davis, and B. R. Bloom. 1985. Genes for the major protein antigens of the leprosy parasite Mycobacterium leprae. Nature316:450-452.","journal-title":"Nature"}],"container-title":["Clinical and Vaccine Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/CVI.13.3.333-340.2006","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/CVI.13.3.333-340.2006","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,6]],"date-time":"2023-05-06T17:50:46Z","timestamp":1683395446000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/CVI.13.3.333-340.2006"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,3]]},"references-count":35,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2006,3]]}},"alternative-id":["10.1128\/CVI.13.3.333-340.2006"],"URL":"https:\/\/doi.org\/10.1128\/cvi.13.3.333-340.2006","relation":{},"ISSN":["1556-6811","1556-679X"],"issn-type":[{"value":"1556-6811","type":"print"},{"value":"1556-679X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,3]]},"assertion":[{"value":"2005-10-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2005-12-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}