Cargando…

Serologic Responses to Recombinant Pneumocystis jirovecii Major Surface Glycoprotein among Ugandan Patients with Respiratory Symptoms

BACKGROUND: Little is known about the serologic responses to Pneumocystis jirovecii major surface glycoprotein (Msg) antigen in African cohorts, or the IgM responses to Msg in HIV-positive and HIV-negative persons with respiratory symptoms. METHODS: We conducted a prospective study of 550 patients,...

Descripción completa

Detalles Bibliográficos
Autores principales: Blount, Robert J., Jarlsberg, Leah G., Daly, Kieran R., Worodria, William, Davis, J. Lucian, Cattamanchi, Adithya, Djawe, Kpandja, Andama, Alfred, Koch, Judith, Walzer, Peter D., Huang, Laurence
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528778/
https://www.ncbi.nlm.nih.gov/pubmed/23284710
http://dx.doi.org/10.1371/journal.pone.0051545
_version_ 1782253869068189696
author Blount, Robert J.
Jarlsberg, Leah G.
Daly, Kieran R.
Worodria, William
Davis, J. Lucian
Cattamanchi, Adithya
Djawe, Kpandja
Andama, Alfred
Koch, Judith
Walzer, Peter D.
Huang, Laurence
author_facet Blount, Robert J.
Jarlsberg, Leah G.
Daly, Kieran R.
Worodria, William
Davis, J. Lucian
Cattamanchi, Adithya
Djawe, Kpandja
Andama, Alfred
Koch, Judith
Walzer, Peter D.
Huang, Laurence
author_sort Blount, Robert J.
collection PubMed
description BACKGROUND: Little is known about the serologic responses to Pneumocystis jirovecii major surface glycoprotein (Msg) antigen in African cohorts, or the IgM responses to Msg in HIV-positive and HIV-negative persons with respiratory symptoms. METHODS: We conducted a prospective study of 550 patients, both HIV-positive (n = 467) and HIV-negative (n = 83), hospitalized with cough ≥2 weeks in Kampala, Uganda, to evaluate the association between HIV status, CD4 cell count, and other clinical predictors and antibody responses to P. jirovecii. We utilized ELISA to measure the IgM and IgG serologic responses to three overlapping recombinant fragments that span the P. jirovecii major surface glycoprotein: MsgA (amino terminus), MsgB (middle portion) and MsgC1 (carboxyl terminus), and to three variations of MsgC1 (MsgC3, MsgC8 and MsgC9). RESULTS: HIV-positive patients demonstrated significantly lower IgM antibody responses to MsgC1, MsgC3, MsgC8 and MsgC9 compared to HIV-negative patients. We found the same pattern of low IgM antibody responses to MsgC1, MsgC3, MsgC8 and MsgC9 among HIV-positive patients with a CD4 cell count <200 cells/µl compared to those with a CD4 cell count ≥200 cells/µl. HIV-positive patients on PCP prophylaxis had significantly lower IgM responses to MsgC3 and MsgC9, and lower IgG responses to MsgA, MsgC1, MsgC3, and MsgC8. In contrast, cigarette smoking was associated with increased IgM antibody responses to MsgC1 and MsgC3 but was not associated with IgG responses. We evaluated IgM and IgG as predictors of mortality. Lower IgM responses to MsgC3 and MsgC8 were both associated with increased in-hospital mortality. CONCLUSIONS: HIV infection and degree of immunosuppression are associated with reduced IgM responses to Msg. In addition, low IgM responses to MsgC3 and MsgC8 are associated with increased mortality.
format Online
Article
Text
id pubmed-3528778
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-35287782013-01-02 Serologic Responses to Recombinant Pneumocystis jirovecii Major Surface Glycoprotein among Ugandan Patients with Respiratory Symptoms Blount, Robert J. Jarlsberg, Leah G. Daly, Kieran R. Worodria, William Davis, J. Lucian Cattamanchi, Adithya Djawe, Kpandja Andama, Alfred Koch, Judith Walzer, Peter D. Huang, Laurence PLoS One Research Article BACKGROUND: Little is known about the serologic responses to Pneumocystis jirovecii major surface glycoprotein (Msg) antigen in African cohorts, or the IgM responses to Msg in HIV-positive and HIV-negative persons with respiratory symptoms. METHODS: We conducted a prospective study of 550 patients, both HIV-positive (n = 467) and HIV-negative (n = 83), hospitalized with cough ≥2 weeks in Kampala, Uganda, to evaluate the association between HIV status, CD4 cell count, and other clinical predictors and antibody responses to P. jirovecii. We utilized ELISA to measure the IgM and IgG serologic responses to three overlapping recombinant fragments that span the P. jirovecii major surface glycoprotein: MsgA (amino terminus), MsgB (middle portion) and MsgC1 (carboxyl terminus), and to three variations of MsgC1 (MsgC3, MsgC8 and MsgC9). RESULTS: HIV-positive patients demonstrated significantly lower IgM antibody responses to MsgC1, MsgC3, MsgC8 and MsgC9 compared to HIV-negative patients. We found the same pattern of low IgM antibody responses to MsgC1, MsgC3, MsgC8 and MsgC9 among HIV-positive patients with a CD4 cell count <200 cells/µl compared to those with a CD4 cell count ≥200 cells/µl. HIV-positive patients on PCP prophylaxis had significantly lower IgM responses to MsgC3 and MsgC9, and lower IgG responses to MsgA, MsgC1, MsgC3, and MsgC8. In contrast, cigarette smoking was associated with increased IgM antibody responses to MsgC1 and MsgC3 but was not associated with IgG responses. We evaluated IgM and IgG as predictors of mortality. Lower IgM responses to MsgC3 and MsgC8 were both associated with increased in-hospital mortality. CONCLUSIONS: HIV infection and degree of immunosuppression are associated with reduced IgM responses to Msg. In addition, low IgM responses to MsgC3 and MsgC8 are associated with increased mortality. Public Library of Science 2012-12-21 /pmc/articles/PMC3528778/ /pubmed/23284710 http://dx.doi.org/10.1371/journal.pone.0051545 Text en © 2012 Blount et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Blount, Robert J.
Jarlsberg, Leah G.
Daly, Kieran R.
Worodria, William
Davis, J. Lucian
Cattamanchi, Adithya
Djawe, Kpandja
Andama, Alfred
Koch, Judith
Walzer, Peter D.
Huang, Laurence
Serologic Responses to Recombinant Pneumocystis jirovecii Major Surface Glycoprotein among Ugandan Patients with Respiratory Symptoms
title Serologic Responses to Recombinant Pneumocystis jirovecii Major Surface Glycoprotein among Ugandan Patients with Respiratory Symptoms
title_full Serologic Responses to Recombinant Pneumocystis jirovecii Major Surface Glycoprotein among Ugandan Patients with Respiratory Symptoms
title_fullStr Serologic Responses to Recombinant Pneumocystis jirovecii Major Surface Glycoprotein among Ugandan Patients with Respiratory Symptoms
title_full_unstemmed Serologic Responses to Recombinant Pneumocystis jirovecii Major Surface Glycoprotein among Ugandan Patients with Respiratory Symptoms
title_short Serologic Responses to Recombinant Pneumocystis jirovecii Major Surface Glycoprotein among Ugandan Patients with Respiratory Symptoms
title_sort serologic responses to recombinant pneumocystis jirovecii major surface glycoprotein among ugandan patients with respiratory symptoms
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528778/
https://www.ncbi.nlm.nih.gov/pubmed/23284710
http://dx.doi.org/10.1371/journal.pone.0051545
work_keys_str_mv AT blountrobertj serologicresponsestorecombinantpneumocystisjiroveciimajorsurfaceglycoproteinamongugandanpatientswithrespiratorysymptoms
AT jarlsbergleahg serologicresponsestorecombinantpneumocystisjiroveciimajorsurfaceglycoproteinamongugandanpatientswithrespiratorysymptoms
AT dalykieranr serologicresponsestorecombinantpneumocystisjiroveciimajorsurfaceglycoproteinamongugandanpatientswithrespiratorysymptoms
AT worodriawilliam serologicresponsestorecombinantpneumocystisjiroveciimajorsurfaceglycoproteinamongugandanpatientswithrespiratorysymptoms
AT davisjlucian serologicresponsestorecombinantpneumocystisjiroveciimajorsurfaceglycoproteinamongugandanpatientswithrespiratorysymptoms
AT cattamanchiadithya serologicresponsestorecombinantpneumocystisjiroveciimajorsurfaceglycoproteinamongugandanpatientswithrespiratorysymptoms
AT djawekpandja serologicresponsestorecombinantpneumocystisjiroveciimajorsurfaceglycoproteinamongugandanpatientswithrespiratorysymptoms
AT andamaalfred serologicresponsestorecombinantpneumocystisjiroveciimajorsurfaceglycoproteinamongugandanpatientswithrespiratorysymptoms
AT kochjudith serologicresponsestorecombinantpneumocystisjiroveciimajorsurfaceglycoproteinamongugandanpatientswithrespiratorysymptoms
AT walzerpeterd serologicresponsestorecombinantpneumocystisjiroveciimajorsurfaceglycoproteinamongugandanpatientswithrespiratorysymptoms
AT huanglaurence serologicresponsestorecombinantpneumocystisjiroveciimajorsurfaceglycoproteinamongugandanpatientswithrespiratorysymptoms
AT serologicresponsestorecombinantpneumocystisjiroveciimajorsurfaceglycoproteinamongugandanpatientswithrespiratorysymptoms