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Clinical and Vaccine Immunology, March 2006, p. 333-340, Vol. 13, No. 3
1071-412X/06/$08.00+0     doi:10.1128/CVI.13.3.333-340.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

ML0405 and ML2331 Are Antigens of Mycobacterium leprae with Potential for Diagnosis of Leprosy

Stephen T. Reece,1 Greg Ireton,1 Raodoh Mohamath,1 Jeffrey Guderian,1 Wakako Goto,1 Robert Gelber,2 Nathan Groathouse,3 John Spencer,3 Patrick Brennan,3 and Steven G. Reed1*

Infectious Disease Research Institute, Seattle, Washington,1 Leonard Wood Memorial Center for Leprosy Research, Cebu City, Philippines,2 Department of Microbiology, Colorado State University, Fort Collins, Colorado3

Received 10 October 2005/ Returned for modification 29 November 2005/ Accepted 21 December 2005

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.

* Corresponding author. Mailing address: IDRI, 1124 Columbia Street, Suite 400, Seattle, WA 98104. Phone: (206) 381-0883. Fax: (206) 381-3678. E-mail: sreed{at}idri.org.

Clinical and Vaccine Immunology, March 2006, p. 333-340, Vol. 13, No. 3
1071-412X/06/$08.00+0     doi:10.1128/CVI.13.3.333-340.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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