Cytokine and protein markers of leprosy reactions in skin and nerves: baseline results for the North Indian INFIR cohort.

BACKGROUND: Previous studies investigating the role of cytokines in the pathogenesis of leprosy have either been on only small numbers of patients or have not combined clinical and histological data. The INFIR Cohort study is a prospective study of 303 new multibacillary leprosy patients to identify...

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Published in:PLoS Neglected Tropical Diseases
Main Authors: Diana N J Lockwood, Lavanya Suneetha, Karuna Devi Sagili, Meher Vani Chaduvula, Ismail Mohammed, Wim van Brakel, W C Smith, Peter Nicholls, Sujai Suneetha
Format: Article in Journal/Newspaper
Language:English
Published: Public Library of Science (PLoS) 2011
Subjects:
Online Access:https://doi.org/10.1371/journal.pntd.0001327
https://doaj.org/article/8ec442deae1446be981ccc5d69d7d751
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spelling ftdoajarticles:oai:doaj.org/article:8ec442deae1446be981ccc5d69d7d751 2023-05-15T15:18:32+02:00 Cytokine and protein markers of leprosy reactions in skin and nerves: baseline results for the North Indian INFIR cohort. Diana N J Lockwood Lavanya Suneetha Karuna Devi Sagili Meher Vani Chaduvula Ismail Mohammed Wim van Brakel W C Smith Peter Nicholls Sujai Suneetha 2011-12-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0001327 https://doaj.org/article/8ec442deae1446be981ccc5d69d7d751 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3236729?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001327 https://doaj.org/article/8ec442deae1446be981ccc5d69d7d751 PLoS Neglected Tropical Diseases, Vol 5, Iss 12, p e1327 (2011) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2011 ftdoajarticles https://doi.org/10.1371/journal.pntd.0001327 2022-12-31T06:34:21Z BACKGROUND: Previous studies investigating the role of cytokines in the pathogenesis of leprosy have either been on only small numbers of patients or have not combined clinical and histological data. The INFIR Cohort study is a prospective study of 303 new multibacillary leprosy patients to identify risk factors for reaction and nerve damage. This study characterised the cellular infiltrate in skin and nerve biopsies using light microscopic and immunohistochemical techniques to identify any association of cytokine markers, nerve and cell markers with leprosy reactions. METHODOLOGY/PRINCIPAL FINDINGS: TNF-α, TGF-β and iNOS protein in skin and nerve biopsies were detected using monoclonal antibody detection immunohistochemistry techniques in 299 skin biopsies and 68 nerve biopsies taken from patients at recruitment. The tissues were stained with hematoxylin and eosin, modified Fite Faraco, CD68 macrophage cell marker and S100. CONCLUSIONS/SIGNIFICANCE: Histological analysis of the biopsies showed that 43% had borderline tuberculoid (BT) leprosy, 27% borderline lepromatous leprosy, 9% lepromatous leprosy, 13% indeterminate leprosy types and 7% had no inflammation. Forty-six percent had histological evidence of a Type 1 Reaction (T1R) and 10% of Erythema Nodosum Leprosum. TNF-α was detected in 78% of skin biopsies (181/232), iNOS in 78% and TGF-β in 94%. All three molecules were detected at higher levels in patients with BT leprosy. TNF-α was localised within macrophages and epithelioid cells in the granuloma, in the epidermis and in dermal nerves in a few cases. TNF-α, iNOS and TGF-β were all significantly associated with T1R (p<0.001). Sixty-eight nerve biopsies were analysed. CD68, TNF-α and iNOS staining were detectable in 88%, 38% and 28% of the biopsies respectively. The three cytokines TNF-α, iNOS and TGF-β detected by immunohistochemistry showed a significant association with the presence of skin reaction. This study is the first to demonstrate an association of iNOS and TGF-β with T1R. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Indian PLoS Neglected Tropical Diseases 5 12 e1327
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
Diana N J Lockwood
Lavanya Suneetha
Karuna Devi Sagili
Meher Vani Chaduvula
Ismail Mohammed
Wim van Brakel
W C Smith
Peter Nicholls
Sujai Suneetha
Cytokine and protein markers of leprosy reactions in skin and nerves: baseline results for the North Indian INFIR cohort.
topic_facet Arctic medicine. Tropical medicine
RC955-962
Public aspects of medicine
RA1-1270
description BACKGROUND: Previous studies investigating the role of cytokines in the pathogenesis of leprosy have either been on only small numbers of patients or have not combined clinical and histological data. The INFIR Cohort study is a prospective study of 303 new multibacillary leprosy patients to identify risk factors for reaction and nerve damage. This study characterised the cellular infiltrate in skin and nerve biopsies using light microscopic and immunohistochemical techniques to identify any association of cytokine markers, nerve and cell markers with leprosy reactions. METHODOLOGY/PRINCIPAL FINDINGS: TNF-α, TGF-β and iNOS protein in skin and nerve biopsies were detected using monoclonal antibody detection immunohistochemistry techniques in 299 skin biopsies and 68 nerve biopsies taken from patients at recruitment. The tissues were stained with hematoxylin and eosin, modified Fite Faraco, CD68 macrophage cell marker and S100. CONCLUSIONS/SIGNIFICANCE: Histological analysis of the biopsies showed that 43% had borderline tuberculoid (BT) leprosy, 27% borderline lepromatous leprosy, 9% lepromatous leprosy, 13% indeterminate leprosy types and 7% had no inflammation. Forty-six percent had histological evidence of a Type 1 Reaction (T1R) and 10% of Erythema Nodosum Leprosum. TNF-α was detected in 78% of skin biopsies (181/232), iNOS in 78% and TGF-β in 94%. All three molecules were detected at higher levels in patients with BT leprosy. TNF-α was localised within macrophages and epithelioid cells in the granuloma, in the epidermis and in dermal nerves in a few cases. TNF-α, iNOS and TGF-β were all significantly associated with T1R (p<0.001). Sixty-eight nerve biopsies were analysed. CD68, TNF-α and iNOS staining were detectable in 88%, 38% and 28% of the biopsies respectively. The three cytokines TNF-α, iNOS and TGF-β detected by immunohistochemistry showed a significant association with the presence of skin reaction. This study is the first to demonstrate an association of iNOS and TGF-β with T1R.
format Article in Journal/Newspaper
author Diana N J Lockwood
Lavanya Suneetha
Karuna Devi Sagili
Meher Vani Chaduvula
Ismail Mohammed
Wim van Brakel
W C Smith
Peter Nicholls
Sujai Suneetha
author_facet Diana N J Lockwood
Lavanya Suneetha
Karuna Devi Sagili
Meher Vani Chaduvula
Ismail Mohammed
Wim van Brakel
W C Smith
Peter Nicholls
Sujai Suneetha
author_sort Diana N J Lockwood
title Cytokine and protein markers of leprosy reactions in skin and nerves: baseline results for the North Indian INFIR cohort.
title_short Cytokine and protein markers of leprosy reactions in skin and nerves: baseline results for the North Indian INFIR cohort.
title_full Cytokine and protein markers of leprosy reactions in skin and nerves: baseline results for the North Indian INFIR cohort.
title_fullStr Cytokine and protein markers of leprosy reactions in skin and nerves: baseline results for the North Indian INFIR cohort.
title_full_unstemmed Cytokine and protein markers of leprosy reactions in skin and nerves: baseline results for the North Indian INFIR cohort.
title_sort cytokine and protein markers of leprosy reactions in skin and nerves: baseline results for the north indian infir cohort.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doi.org/10.1371/journal.pntd.0001327
https://doaj.org/article/8ec442deae1446be981ccc5d69d7d751
geographic Arctic
Indian
geographic_facet Arctic
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genre Arctic
genre_facet Arctic
op_source PLoS Neglected Tropical Diseases, Vol 5, Iss 12, p e1327 (2011)
op_relation http://europepmc.org/articles/PMC3236729?pdf=render
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1935-2727
1935-2735
doi:10.1371/journal.pntd.0001327
https://doaj.org/article/8ec442deae1446be981ccc5d69d7d751
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container_title PLoS Neglected Tropical Diseases
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