Differential immunoglobulin and complement levels in leprosy prior to development of reversal reaction and erythema nodosum leprosum.
BACKGROUND:Leprosy is a treatable infectious disease caused by Mycobacterium leprae. However, there is additional morbidity from leprosy-associated pathologic immune reactions, reversal reaction (RR) and erythema nodosum leprosum (ENL), which occur in 1 in 3 people with leprosy, even with effective...
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Online Access: | https://doi.org/10.1371/journal.pntd.0007089 https://doaj.org/article/2947fb8cac1f4fc3a7ce1dc741e76742 |
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ftdoajarticles:oai:doaj.org/article:2947fb8cac1f4fc3a7ce1dc741e76742 2023-05-15T15:16:48+02:00 Differential immunoglobulin and complement levels in leprosy prior to development of reversal reaction and erythema nodosum leprosum. Francianne M Amorim Maurício L Nobre Larissa S Nascimento Alesson M Miranda Glória R G Monteiro Francisco P Freire-Neto Maria do Carmo Palmeira Queiroz José W Queiroz Malcolm S Duthie Marcos R Costa Steven G Reed Warren D Johnson Kathryn M Dupnik Selma M B Jeronimo 2019-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0007089 https://doaj.org/article/2947fb8cac1f4fc3a7ce1dc741e76742 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC6366718?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0007089 https://doaj.org/article/2947fb8cac1f4fc3a7ce1dc741e76742 PLoS Neglected Tropical Diseases, Vol 13, Iss 1, p e0007089 (2019) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2019 ftdoajarticles https://doi.org/10.1371/journal.pntd.0007089 2022-12-31T02:26:47Z BACKGROUND:Leprosy is a treatable infectious disease caused by Mycobacterium leprae. However, there is additional morbidity from leprosy-associated pathologic immune reactions, reversal reaction (RR) and erythema nodosum leprosum (ENL), which occur in 1 in 3 people with leprosy, even with effective treatment of M. leprae. There is currently no predictive marker in use to indicate which people with leprosy will develop these debilitating immune reactions. Our peripheral blood mononuclear cell (PBMC) transcriptome analysis revealed that activation of the classical complement pathway is common to both RR and ENL. Additionally, differential expression of immunoglobulin receptors and B cell receptors during RR and ENL support a role for the antibody-mediated immune response during both RR and ENL. In this study, we investigated B-cell immunophenotypes, total and M. leprae-specific antibodies, and complement levels in leprosy patients with and without RR or ENL. The objective was to determine the role of these immune mediators in pathogenesis and assess their potential as biomarkers of risk for immune reactions in people with leprosy. METHODOLOGY/FINDINGS:We followed newly diagnosed leprosy cases (n = 96) for two years for development of RR or ENL. They were compared with active RR (n = 35), active ENL (n = 29), and healthy household contacts (n = 14). People with leprosy who subsequently developed ENL had increased IgM, IgG1, and C3d-associated immune complexes with decreased complement 4 (C4) at leprosy diagnosis. People who developed RR also had decreased C4 at leprosy diagnosis. Additionally, elevated anti-M. leprae antibody levels were associated with subsequent RR or ENL. CONCLUSIONS:Differential co-receptor expression and immunoglobulin levels before and during immune reactions intimate a central role for humoral immunity in RR and ENL. Decreased C4 and elevated anti-M. leprae antibodies in people with new diagnosis of leprosy may be risk factors for subsequent development of leprosy immune reactions. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 13 1 e0007089 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Francianne M Amorim Maurício L Nobre Larissa S Nascimento Alesson M Miranda Glória R G Monteiro Francisco P Freire-Neto Maria do Carmo Palmeira Queiroz José W Queiroz Malcolm S Duthie Marcos R Costa Steven G Reed Warren D Johnson Kathryn M Dupnik Selma M B Jeronimo Differential immunoglobulin and complement levels in leprosy prior to development of reversal reaction and erythema nodosum leprosum. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND:Leprosy is a treatable infectious disease caused by Mycobacterium leprae. However, there is additional morbidity from leprosy-associated pathologic immune reactions, reversal reaction (RR) and erythema nodosum leprosum (ENL), which occur in 1 in 3 people with leprosy, even with effective treatment of M. leprae. There is currently no predictive marker in use to indicate which people with leprosy will develop these debilitating immune reactions. Our peripheral blood mononuclear cell (PBMC) transcriptome analysis revealed that activation of the classical complement pathway is common to both RR and ENL. Additionally, differential expression of immunoglobulin receptors and B cell receptors during RR and ENL support a role for the antibody-mediated immune response during both RR and ENL. In this study, we investigated B-cell immunophenotypes, total and M. leprae-specific antibodies, and complement levels in leprosy patients with and without RR or ENL. The objective was to determine the role of these immune mediators in pathogenesis and assess their potential as biomarkers of risk for immune reactions in people with leprosy. METHODOLOGY/FINDINGS:We followed newly diagnosed leprosy cases (n = 96) for two years for development of RR or ENL. They were compared with active RR (n = 35), active ENL (n = 29), and healthy household contacts (n = 14). People with leprosy who subsequently developed ENL had increased IgM, IgG1, and C3d-associated immune complexes with decreased complement 4 (C4) at leprosy diagnosis. People who developed RR also had decreased C4 at leprosy diagnosis. Additionally, elevated anti-M. leprae antibody levels were associated with subsequent RR or ENL. CONCLUSIONS:Differential co-receptor expression and immunoglobulin levels before and during immune reactions intimate a central role for humoral immunity in RR and ENL. Decreased C4 and elevated anti-M. leprae antibodies in people with new diagnosis of leprosy may be risk factors for subsequent development of leprosy immune reactions. |
format |
Article in Journal/Newspaper |
author |
Francianne M Amorim Maurício L Nobre Larissa S Nascimento Alesson M Miranda Glória R G Monteiro Francisco P Freire-Neto Maria do Carmo Palmeira Queiroz José W Queiroz Malcolm S Duthie Marcos R Costa Steven G Reed Warren D Johnson Kathryn M Dupnik Selma M B Jeronimo |
author_facet |
Francianne M Amorim Maurício L Nobre Larissa S Nascimento Alesson M Miranda Glória R G Monteiro Francisco P Freire-Neto Maria do Carmo Palmeira Queiroz José W Queiroz Malcolm S Duthie Marcos R Costa Steven G Reed Warren D Johnson Kathryn M Dupnik Selma M B Jeronimo |
author_sort |
Francianne M Amorim |
title |
Differential immunoglobulin and complement levels in leprosy prior to development of reversal reaction and erythema nodosum leprosum. |
title_short |
Differential immunoglobulin and complement levels in leprosy prior to development of reversal reaction and erythema nodosum leprosum. |
title_full |
Differential immunoglobulin and complement levels in leprosy prior to development of reversal reaction and erythema nodosum leprosum. |
title_fullStr |
Differential immunoglobulin and complement levels in leprosy prior to development of reversal reaction and erythema nodosum leprosum. |
title_full_unstemmed |
Differential immunoglobulin and complement levels in leprosy prior to development of reversal reaction and erythema nodosum leprosum. |
title_sort |
differential immunoglobulin and complement levels in leprosy prior to development of reversal reaction and erythema nodosum leprosum. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2019 |
url |
https://doi.org/10.1371/journal.pntd.0007089 https://doaj.org/article/2947fb8cac1f4fc3a7ce1dc741e76742 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 13, Iss 1, p e0007089 (2019) |
op_relation |
http://europepmc.org/articles/PMC6366718?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0007089 https://doaj.org/article/2947fb8cac1f4fc3a7ce1dc741e76742 |
op_doi |
https://doi.org/10.1371/journal.pntd.0007089 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
13 |
container_issue |
1 |
container_start_page |
e0007089 |
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1766347090150031360 |