Utility of immunoglobulin isotypes against LID-1 and NDO-LID for, particularly IgG1, confirming the diagnosis of multibacillary leprosy

BACKGROUND Leprosy remains a health problem in many countries, with difficulties in diagnosis resulting in delayed treatment and more severe disabilities. Antibodies against several Mycobacterium leprae antigens have, however, shown value as diagnostic and/or prognostic markers. OBJECTIVES The ob...

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Main Authors: Pedro Henrique Ferreira Marçal, Lúcia Alves de Oliveira Fraga, Ana Márcia Menezes de Mattos, Laura Menegati, Angélica da Conceição Oliveira Coelho, Roberta Olmo Pinheiro, Euzenir Nunes Sarno, Malcolm S Duthie, Henrique Couto Teixeira
Format: Article
Language:English
Published: Fundação Oswaldo Cruz (FIOCRUZ) 2018-02-01
Series:Memorias do Instituto Oswaldo Cruz
Subjects:
Online Access:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762018000500301&lng=en&tlng=en
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author Pedro Henrique Ferreira Marçal
Lúcia Alves de Oliveira Fraga
Ana Márcia Menezes de Mattos
Laura Menegati
Angélica da Conceição Oliveira Coelho
Roberta Olmo Pinheiro
Euzenir Nunes Sarno
Malcolm S Duthie
Henrique Couto Teixeira
author_facet Pedro Henrique Ferreira Marçal
Lúcia Alves de Oliveira Fraga
Ana Márcia Menezes de Mattos
Laura Menegati
Angélica da Conceição Oliveira Coelho
Roberta Olmo Pinheiro
Euzenir Nunes Sarno
Malcolm S Duthie
Henrique Couto Teixeira
author_sort Pedro Henrique Ferreira Marçal
collection DOAJ
description BACKGROUND Leprosy remains a health problem in many countries, with difficulties in diagnosis resulting in delayed treatment and more severe disabilities. Antibodies against several Mycobacterium leprae antigens have, however, shown value as diagnostic and/or prognostic markers. OBJECTIVES The objective of this study was to evaluate serum immunoglobulin (Ig) IgM and IgG subclass reactivity against three M. leprae specific antigens: NDO-HSA, a conjugate formed by natural octyl disaccharide bound to human serum albumin; LID-1, the fusion protein product of the ml0405 and ml2331 genes; and NDO-LID, a combination of LID-1 and NDO. METHODS Sera from healthy controls, paucibacillary (PB) and multibacillary (MB) leprosy patients, and their respective household contacts, were evaluated for the presence of antigen-specific IgM, IgG, and IgG subclass antibodies by enzyme-linked immunosorbent assay (ELISA). The sensitivity and specificity of each ELISA were evaluated by receiver operating characteristic (ROC) curve analysis. FINDINGS Our data confirm that serum IgM antibodies against NDO-HSA and IgG antibodies against LID-1, as well as IgG/M antibodies against NDO-LID, are markedly increased in MB patients. For the first time, our data reveal a selective increase in IgG1 and IgG3 antibodies against LID-1 and NDO-LID in MB patients, demonstrating that these antibody isotypes are suitable for differentiation between MB and PB patients. ROC curve analysis indicates an improved capacity for diagnosing MB leprosy patients using the detection of IgG antibodies, particularly the IgG1 isotype, specific to LID-1 and NDO-LID over the performance levels attained with NDO-HSA. CONCLUSIONS Our findings indicate that serological tests based on the detection of antigen-specific IgG1 antibodies are a useful tool to differentiate MB from PB patients, and indicate the enhanced performance of the LID-1 and NDO-LID antigens in the serodiagnosis of leprosy.
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spelling doaj.art-59ef77a8007e45d9a05ff59778b4be752023-09-02T22:10:59ZengFundação Oswaldo Cruz (FIOCRUZ)Memorias do Instituto Oswaldo Cruz1678-80602018-02-01113510.1590/0074-02760170467S0074-02762018000500301Utility of immunoglobulin isotypes against LID-1 and NDO-LID for, particularly IgG1, confirming the diagnosis of multibacillary leprosyPedro Henrique Ferreira MarçalLúcia Alves de Oliveira FragaAna Márcia Menezes de MattosLaura MenegatiAngélica da Conceição Oliveira CoelhoRoberta Olmo PinheiroEuzenir Nunes SarnoMalcolm S DuthieHenrique Couto TeixeiraBACKGROUND Leprosy remains a health problem in many countries, with difficulties in diagnosis resulting in delayed treatment and more severe disabilities. Antibodies against several Mycobacterium leprae antigens have, however, shown value as diagnostic and/or prognostic markers. OBJECTIVES The objective of this study was to evaluate serum immunoglobulin (Ig) IgM and IgG subclass reactivity against three M. leprae specific antigens: NDO-HSA, a conjugate formed by natural octyl disaccharide bound to human serum albumin; LID-1, the fusion protein product of the ml0405 and ml2331 genes; and NDO-LID, a combination of LID-1 and NDO. METHODS Sera from healthy controls, paucibacillary (PB) and multibacillary (MB) leprosy patients, and their respective household contacts, were evaluated for the presence of antigen-specific IgM, IgG, and IgG subclass antibodies by enzyme-linked immunosorbent assay (ELISA). The sensitivity and specificity of each ELISA were evaluated by receiver operating characteristic (ROC) curve analysis. FINDINGS Our data confirm that serum IgM antibodies against NDO-HSA and IgG antibodies against LID-1, as well as IgG/M antibodies against NDO-LID, are markedly increased in MB patients. For the first time, our data reveal a selective increase in IgG1 and IgG3 antibodies against LID-1 and NDO-LID in MB patients, demonstrating that these antibody isotypes are suitable for differentiation between MB and PB patients. ROC curve analysis indicates an improved capacity for diagnosing MB leprosy patients using the detection of IgG antibodies, particularly the IgG1 isotype, specific to LID-1 and NDO-LID over the performance levels attained with NDO-HSA. CONCLUSIONS Our findings indicate that serological tests based on the detection of antigen-specific IgG1 antibodies are a useful tool to differentiate MB from PB patients, and indicate the enhanced performance of the LID-1 and NDO-LID antigens in the serodiagnosis of leprosy.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762018000500301&lng=en&tlng=enleprosyserodiagnosisM. leprae antigenLID-1natural octyl disaccharideIgG1 immunoglobulin subclass
spellingShingle Pedro Henrique Ferreira Marçal
Lúcia Alves de Oliveira Fraga
Ana Márcia Menezes de Mattos
Laura Menegati
Angélica da Conceição Oliveira Coelho
Roberta Olmo Pinheiro
Euzenir Nunes Sarno
Malcolm S Duthie
Henrique Couto Teixeira
Utility of immunoglobulin isotypes against LID-1 and NDO-LID for, particularly IgG1, confirming the diagnosis of multibacillary leprosy
Memorias do Instituto Oswaldo Cruz
leprosy
serodiagnosis
M. leprae antigen
LID-1
natural octyl disaccharide
IgG1 immunoglobulin subclass
title Utility of immunoglobulin isotypes against LID-1 and NDO-LID for, particularly IgG1, confirming the diagnosis of multibacillary leprosy
title_full Utility of immunoglobulin isotypes against LID-1 and NDO-LID for, particularly IgG1, confirming the diagnosis of multibacillary leprosy
title_fullStr Utility of immunoglobulin isotypes against LID-1 and NDO-LID for, particularly IgG1, confirming the diagnosis of multibacillary leprosy
title_full_unstemmed Utility of immunoglobulin isotypes against LID-1 and NDO-LID for, particularly IgG1, confirming the diagnosis of multibacillary leprosy
title_short Utility of immunoglobulin isotypes against LID-1 and NDO-LID for, particularly IgG1, confirming the diagnosis of multibacillary leprosy
title_sort utility of immunoglobulin isotypes against lid 1 and ndo lid for particularly igg1 confirming the diagnosis of multibacillary leprosy
topic leprosy
serodiagnosis
M. leprae antigen
LID-1
natural octyl disaccharide
IgG1 immunoglobulin subclass
url http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762018000500301&lng=en&tlng=en
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