Quantitative lateral flow strip assays as User-Friendly Tools To Detect Biomarker Profiles For Leprosy.

Anouk Van Hooij,Roel Faber,Claudia J De Dood,Jan Hendrik Richardus,Elisa M Tjon Kon Fat,Renate Richardus,Korshed Alam,Louis Wilson,Susan J F Van Den Eeden,Paul L A M Corstjens,Annemieke Geluk

doi:10.1038/srep34260

Anouk Van Hooij, Roel Faber + Show 9 more

Open Access

https://doi.org/10.1038/srep34260

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Journal: Scientific Reports	Publication Date: Sep 29, 2016
Citations: 49	License type: CC BY 4.0

Affiliation: Leiden University Medical Center, Erasmus MC

Abstract

Leprosy is a debilitating, infectious disease caused by Mycobacterium leprae. Despite the availability of multidrug therapy, transmission is unremitting. Thus, early identification of M. leprae infection is essential to reduce transmission. The immune response to M. leprae is determined by host genetics, resulting in paucibacillary (PB) and multibacillary (MB) leprosy associated with dominant cellular or humoral immunity, respectively. This spectral pathology of leprosy compels detection of immunity to M. leprae to be based on multiple, diverse biomarkers. In this study we have applied quantitative user friendly lateral flow assays (LFAs) for four immune markers (anti-PGL-I antibodies, IL-10, CCL4 and IP-10) for whole blood samples from a longitudinal BCG vaccination field-trial in Bangladesh. Different biomarker profiles, in contrast to single markers, distinguished M. leprae infected from non-infected test groups, patients from household contacts (HHC) and endemic controls (EC), or MB from PB patients. The test protocol presented in this study merging detection of innate, adaptive cellular as well as humoral immunity, thus provides a convenient tool to measure specific biomarker profiles for M. leprae infection and leprosy utilizing a field-friendly technology.

Highlights

Leprosy, a chronic infectious disease caused by Mycobacterium leprae (M. leprae) ranking second as the most pathogenic mycobacterial infectious disease after tuberculosis (TB), is still considered a major threat in developing countries[1]
We demonstrated that chemokine (C-C motif) ligand 4 (CCL4), a component of the innate immunity, can be used to identify pathogenic immunity against M. leprae since it was increased in patients, partly in household contacts but not in endemic controls[16]
IL-10, inducible protein 10 (IP-10) and CCL4 levels were determined in Nil, whole cell sonicate (WCS) and Mlep samples, as well as anti-phenolic glycolipid I (PGL-I) IgM levels (Fig. 1)

Summary

Introduction

A chronic infectious disease caused by Mycobacterium leprae (M. leprae) ranking second as the most pathogenic mycobacterial infectious disease after tuberculosis (TB), is still considered a major threat in developing countries[1]. Molecular techniques to elicit strain differences within the leprosy bacillus are important diagnostic tools to enhance our understanding of the epidemiology of leprosy, differentiate between relapse and re-infection[6,7,8,9,10], these pathogen-derived profiles are not suitable to indicate development of leprosy in infected, asymptomatic individuals These hurdles contributed to the current lack of tests for detection of asymptomatic M. leprae infection and diagnosis of early stage leprosy[11]. Tests based on multicomponent host biomarker profiles that can identify M. leprae infected individuals (yet) without clinical symptoms of leprosy, will be useful for guidance of prophylactic treatment, thereby contributing to reduction of M. leprae transmission as well as prevention of disabilities

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