IgG3 and IL10 are effective biomarkers for monitoring therapeutic effectiveness in Post Kala-Azar Dermal Leishmaniasis

<h4>Background</h4> The assessment of chemotherapeutic responses in Post Kala-azar Dermal Leishmaniasis (PKDL), especially its macular form is challenging, emphasizing the necessity for ‘test of cure’ tools. This study explored the diagnostic and prognostic potential of IgG subclasses an...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Shilpa Sengupta, Mitali Chatterjee
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/d7de19ca73974424a8c3fb38fb4b0ad2
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:d7de19ca73974424a8c3fb38fb4b0ad2
record_format	dspace
spelling	oai:doaj.org-article:d7de19ca73974424a8c3fb38fb4b0ad22021-11-18T09:14:50ZIgG3 and IL10 are effective biomarkers for monitoring therapeutic effectiveness in Post Kala-Azar Dermal Leishmaniasis1935-27271935-2735https://doaj.org/article/d7de19ca73974424a8c3fb38fb4b0ad22021-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8580238/?tool=EBIhttps://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735<h4>Background</h4> The assessment of chemotherapeutic responses in Post Kala-azar Dermal Leishmaniasis (PKDL), especially its macular form is challenging, emphasizing the necessity for ‘test of cure’ tools. This study explored the diagnostic and prognostic potential of IgG subclasses and associated cytokines for monitoring the effectiveness of chemotherapy in PKDL. <h4>Methods</h4> Participants included PKDL cases at (a) disease presentation, (b) immediately at the end of treatment (12 weeks for Miltefosine or 3 weeks for Liposomal Amphotericin B, LAmB and (c) at any time point 6 months later, for estimating anti-leishmanial immunoglobulin (Ig, IgG, IgM, IgG1, IgG2 and IgG3) and cytokines (IL-10, IL-6). <h4>Results</h4> In PKDL, Ig levels were elevated, with IgG3 and IL-10 being the major contributors. Miltefosine decreased both markers substantially and this decrease was sustained for at least six months. In contrast, LAmB failed to decrease IgG3 and IL-10, as even after six months, their levels remained unchanged or even increased. <h4>Conclusions</h4> In PKDL, IgG3 and IL-10 proved to be effective predictors of responsiveness to chemotherapy and may be considered as a non invasive alternative for longitudinal monitoring. Author summary Post Kala-azar Dermal Leishmaniasis (PKDL) is a dermal condition that occurs in East Africa and South Asia, the latter in 5–10% of patients after apparent cure from Visceral Leishmaniasis (VL). Till date, conventional knowledge in South Asia was that the polymorphic form of PKDL comprising of macules, papules and nodules was the predominant disease form, constituting 85–90%. However, since 2014, implementation of active-case surveillance led to unearthing of a large number of macular, hypopigmented cases, and was reported to contribute to nearly 50% of the disease burden. In particular, the macular form poses a diagnostic dilemma as microscopically parasites are difficult to identify in their lesions, and repigmentation occurs months after parasite clearance, emphasizing the need for developing non-invasive approaches for measurement of parasite burden. Till date, no formal clinical trial for treatment of PKDL has been undertaken where the parasite load was quantified and treatment remains empirical. This is primarily due to PKDL cases being unwilling to provide a repeat skin biopsy once their lesions have declined. Therefore, in cases where treatment failure occurs, it cannot be precisely identified, and could potentially lead to these cases becoming mobile disease reservoirs, thereby adversely impacting on the ongoing VL elimination programme. This study addressed this critical lacuna, where it was established that in both clinical types of PKDL, circulating levels of IgG3 and IL-10 can be considered as effective markers for monitoring treatment outcome. At disease presentation, the raised levels of IgG subclasses and associated cytokines (IL-10 and IL-6) declined following therapy with Miltefosine, the maximum decrease being with IgG3 along with IL-10; importantly, this decrease was sustained for at least six months. In contrast, LAmB failed to decrease the levels of immunoglobulins and associated cytokines even six months after completion of treatment; in fact the antibody levels either increased or remained unchanged. Taken together, this study has established the potential of IgG3 and IL10 as a non-invasive alternative for monitoring of chemotherapeutic responses in PKDL.Shilpa SenguptaMitali ChatterjeePublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 15, Iss 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
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 Shilpa Sengupta Mitali Chatterjee IgG3 and IL10 are effective biomarkers for monitoring therapeutic effectiveness in Post Kala-Azar Dermal Leishmaniasis
description	<h4>Background</h4> The assessment of chemotherapeutic responses in Post Kala-azar Dermal Leishmaniasis (PKDL), especially its macular form is challenging, emphasizing the necessity for ‘test of cure’ tools. This study explored the diagnostic and prognostic potential of IgG subclasses and associated cytokines for monitoring the effectiveness of chemotherapy in PKDL. <h4>Methods</h4> Participants included PKDL cases at (a) disease presentation, (b) immediately at the end of treatment (12 weeks for Miltefosine or 3 weeks for Liposomal Amphotericin B, LAmB and (c) at any time point 6 months later, for estimating anti-leishmanial immunoglobulin (Ig, IgG, IgM, IgG1, IgG2 and IgG3) and cytokines (IL-10, IL-6). <h4>Results</h4> In PKDL, Ig levels were elevated, with IgG3 and IL-10 being the major contributors. Miltefosine decreased both markers substantially and this decrease was sustained for at least six months. In contrast, LAmB failed to decrease IgG3 and IL-10, as even after six months, their levels remained unchanged or even increased. <h4>Conclusions</h4> In PKDL, IgG3 and IL-10 proved to be effective predictors of responsiveness to chemotherapy and may be considered as a non invasive alternative for longitudinal monitoring. Author summary Post Kala-azar Dermal Leishmaniasis (PKDL) is a dermal condition that occurs in East Africa and South Asia, the latter in 5–10% of patients after apparent cure from Visceral Leishmaniasis (VL). Till date, conventional knowledge in South Asia was that the polymorphic form of PKDL comprising of macules, papules and nodules was the predominant disease form, constituting 85–90%. However, since 2014, implementation of active-case surveillance led to unearthing of a large number of macular, hypopigmented cases, and was reported to contribute to nearly 50% of the disease burden. In particular, the macular form poses a diagnostic dilemma as microscopically parasites are difficult to identify in their lesions, and repigmentation occurs months after parasite clearance, emphasizing the need for developing non-invasive approaches for measurement of parasite burden. Till date, no formal clinical trial for treatment of PKDL has been undertaken where the parasite load was quantified and treatment remains empirical. This is primarily due to PKDL cases being unwilling to provide a repeat skin biopsy once their lesions have declined. Therefore, in cases where treatment failure occurs, it cannot be precisely identified, and could potentially lead to these cases becoming mobile disease reservoirs, thereby adversely impacting on the ongoing VL elimination programme. This study addressed this critical lacuna, where it was established that in both clinical types of PKDL, circulating levels of IgG3 and IL-10 can be considered as effective markers for monitoring treatment outcome. At disease presentation, the raised levels of IgG subclasses and associated cytokines (IL-10 and IL-6) declined following therapy with Miltefosine, the maximum decrease being with IgG3 along with IL-10; importantly, this decrease was sustained for at least six months. In contrast, LAmB failed to decrease the levels of immunoglobulins and associated cytokines even six months after completion of treatment; in fact the antibody levels either increased or remained unchanged. Taken together, this study has established the potential of IgG3 and IL10 as a non-invasive alternative for monitoring of chemotherapeutic responses in PKDL.
format	article
author	Shilpa Sengupta Mitali Chatterjee
author_facet	Shilpa Sengupta Mitali Chatterjee
author_sort	Shilpa Sengupta
title	IgG3 and IL10 are effective biomarkers for monitoring therapeutic effectiveness in Post Kala-Azar Dermal Leishmaniasis
title_short	IgG3 and IL10 are effective biomarkers for monitoring therapeutic effectiveness in Post Kala-Azar Dermal Leishmaniasis
title_full	IgG3 and IL10 are effective biomarkers for monitoring therapeutic effectiveness in Post Kala-Azar Dermal Leishmaniasis
title_fullStr	IgG3 and IL10 are effective biomarkers for monitoring therapeutic effectiveness in Post Kala-Azar Dermal Leishmaniasis
title_full_unstemmed	IgG3 and IL10 are effective biomarkers for monitoring therapeutic effectiveness in Post Kala-Azar Dermal Leishmaniasis
title_sort	igg3 and il10 are effective biomarkers for monitoring therapeutic effectiveness in post kala-azar dermal leishmaniasis
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/d7de19ca73974424a8c3fb38fb4b0ad2
work_keys_str_mv	AT shilpasengupta igg3andil10areeffectivebiomarkersformonitoringtherapeuticeffectivenessinpostkalaazardermalleishmaniasis AT mitalichatterjee igg3andil10areeffectivebiomarkersformonitoringtherapeuticeffectivenessinpostkalaazardermalleishmaniasis
_version_	1718420993049886720

IgG3 and IL10 are effective biomarkers for monitoring therapeutic effectiveness in Post Kala-Azar Dermal Leishmaniasis

Ejemplares similares