title: Identification of serological biomarkers of infection, disease progression and treatment efficacy for leprosy.
abstract: Although leprosy is curable with drug treatment, the identification of biomarkers of infection, disease progression and treatment efficacy would greatly help to reduce the overall prevalence of the disease. Reliable biomarkers would also reduce the incidence of grade-2 disability by ensuring that those who are most at risk are diagnosed and treated early or offered repeated treatments in the case of relapse. In this study, we examined the reactivity of sera from lepromatous and tuberculoid leprosy patients (LPs) against a panel of 12 recombinant Mycobacterium leprae proteins and found that six proteins were strongly recognised by multibacillary (MB) patients, while only three were consistently recognised by paucibacillary patients. To better understand the dynamics of patient antibody responses during and after drug therapy, we measured antibody titres to four recombinant proteins, phenolic glycolipid-I and lipoarabinomannan at baseline and up to two years after diagnosis to investigate the temporal changes in the antibody titres. Reactivity patterns to individual antigens and decreases in antibody titres were patient-specific. Antibody titres to proteins declined more rapidly vs. those to carbohydrate and glycolipid antigens. Compared to baseline values, increases in antibody titres were observed during reactional episodes in one individual. Additionally, antibody responses against a subset of antigens that provided a good prognostic indicator of disease progression were analysed in 51 household contacts of MB index cases for up to two years. Although the majority of these contacts showed no change or exhibited decreases in antibody titres, seven individuals developed higher titres towards one or more of these antigens and one individual with progressively higher titres was diagnosed with borderline lepromatous leprosy 19 months after enrolment. The results of this study indicate that antibody titres to specific M. leprae antigens can be used to monitor treatment efficacy in LPs and assess disease progression in those most at risk for developing this disease.
authors.affiliation: Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, USA. john.spencer@colostate.edu
authors.forename: John S
authors.initials: JS
authors.lastname: Spencer
authors.forename: Malcolm S
authors.initials: MS
authors.lastname: Duthie
authors.forename: Annemieke
authors.initials: A
authors.lastname: Geluk
authors.forename: Marivic F
authors.initials: MF
authors.lastname: Balagon
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: William H
authors.initials: WH
authors.lastname: Wheat
authors.forename: Delphi
authors.initials: D
authors.lastname: Chatterjee
authors.forename: Mary
authors.initials: M
authors.lastname: Jackson
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Jade N
authors.initials: JN
authors.lastname: Kurihara
authors.forename: Armi
authors.initials: A
authors.lastname: Maghanoy
authors.forename: Irene
authors.initials: I
authors.lastname: Mallari
authors.forename: Paul
authors.initials: P
authors.lastname: Saunderson
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Brennan
authors.forename: Hazel M
authors.initials: HM
authors.lastname: Dockrell
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000907:Antibodies, Bacterial / Q000097:blood*; D000942:Antigens, Bacterial / Q000097:blood*; D001426:Bacterial Proteins / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002648:Child; D004185:Disability Evaluation; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005191:Family Characteristics; D005260:Female; D006017:Glycolipids / Q000097:blood*; D006801:Humans; D007918:Leprosy / Q000097:blood / Q000175:diagnosis*; D008070:Lipopolysaccharides / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009166:Mycobacterium leprae / Q000276:immunology*; D011994:Recombinant Proteins / Q000097:blood; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D015415:Biomarkers; D006017:Glycolipids; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; C050016:lipoarabinomannan; C045169:phenolic glycolipid I, Mycobacterium leprae