title: Use of protein antigens for early serological diagnosis of leprosy.
abstract: Leprosy is a chronic and debilitating human disease caused by infection with the Mycobacterium leprae bacillus. Despite the marked reduction in the number of registered worldwide leprosy cases as a result of the widespread use of multidrug therapy, the number of new cases detected each year remains relatively stable. This indicates that M. leprae is still being transmitted and that, without earlier diagnosis, M. leprae infection will continue to pose a health problem. Current diagnostic techniques, based on the appearance of clinical symptoms or of immunoglobulin M (IgM) antibodies that recognize the bacterial phenolic glycolipid I, are unable to reliably identify early-stage leprosy. In this study we examine the ability of IgG within leprosy patient sera to bind several M. leprae protein antigens. As expected, multibacillary leprosy patients provided stronger responses than paucibacillary leprosy patients. We demonstrate that the geographic locations of the patients can influence the antigens they recognize but that ML0405 and ML2331 are recognized by sera from diverse regions (the Philippines, coastal and central Brazil, and Japan). A fusion construct of these two proteins (designated leprosy IDRI diagnostic 1 [LID-1]) retained the diagnostic activity of the component antigens. Upon testing against a panel of prospective sera from individuals who developed leprosy, we determined that LID-1 was capable of diagnosing leprosy 6 to 8 months before the onset of clinical symptoms. A serological diagnostic test capable of identifying and allowing treatment of early-stage leprosy could reduce transmission, prevent functional disabilities and stigmatizing deformities, and facilitate leprosy eradication.
authors: Infectious Disease Research Institute, 1124 Columbia St., Suite 400, Seattle, WA 98104, USA. mduthie@idri.org
authors: Malcolm S
authors: MS
authors: Duthie
authors: Wakako
authors: W
authors: Goto
authors: Greg C
authors: GC
authors: Ireton
authors: Stephen T
authors: ST
authors: Reece
authors: Ludimila P V
authors: LP
authors: Cardoso
authors: Celina M T
authors: CM
authors: Martelli
authors: Mariane M A
authors: MM
authors: Stefani
authors: Maria
authors: M
authors: Nakatani
authors: Robson Crusue
authors: RC
authors: de Jesus
authors: Eduardo M
authors: EM
authors: Netto
authors: Ma V F
authors: MV
authors: Balagon
authors: Esterlina
authors: E
authors: Tan
authors: Robert H
authors: RH
authors: Gelber
authors: Yumi
authors: Y
authors: Maeda
authors: Masahiko
authors: M
authors: Makino
authors: Dan
authors: D
authors: Hoft
authors: Steven G
authors: SG
authors: Reed
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000907:Antibodies, Bacterial / Q000097:blood* / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D002648:Child; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D007918:Leprosy / Q000175:diagnosis* / Q000276:immunology* / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D009166:Mycobacterium leprae / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011993:Recombinant Fusion Proteins