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

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. We conducted a prospective study of 550 patients, both HIV-positive (n...

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Vydáno v:	PloS one Ročník 7; číslo 12; s. e51545
Hlavní autoři:	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
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Public Library of Science 21.12.2012 Public Library of Science (PLoS)
Témata:	Acquired immune deficiency syndrome Adolescent Adult AIDS AIDS-Related Opportunistic Infections - blood AIDS-Related Opportunistic Infections - immunology AIDS-Related Opportunistic Infections - microbiology Antibodies, Fungal - blood Antigens Biology Biomarkers - blood CD4 antigen Cigarette smoking Collaboration Cough Critical care Cross infection Environmental health Enzyme-Linked Immunosorbent Assay Epidemiology Female Fungal Proteins - blood Fungal Proteins - genetics Fungal Proteins - immunology Gene expression Glycoproteins HIV HIV - pathogenicity HIV Infections - complications HIV Infections - microbiology HIV Infections - virology Hospital Mortality Hospital patients Hospitals Human immunodeficiency virus Humans Immunoglobulin G Immunoglobulin G - blood Immunoglobulin G - immunology Immunoglobulin M Immunoglobulin M - blood Immunoglobulin M - immunology Immunology Immunosuppression Infections Infectious diseases Internal medicine Male Medical diagnosis Medical research Medicine Membrane Glycoproteins - blood Membrane Glycoproteins - genetics Membrane Glycoproteins - immunology Middle Aged Mortality Patients Pneumocystis carinii - immunology Pneumonia Pneumonia, Pneumocystis - blood Pneumonia, Pneumocystis - immunology Pneumonia, Pneumocystis - microbiology Prophylaxis Prospective Studies Recombinant Proteins - blood Recombinant Proteins - genetics Recombinant Proteins - immunology Respiratory symptoms Risk Factors Smoking Studies Tuberculosis Uganda Young Adult Uganda San Francisco California Ohio California United States > US Kampala Uganda
ISSN:	1932-6203, 1932-6203
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Shrnutí:	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. 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). 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. 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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Competing Interests: The authors have declared that no competing interests exist. Conceived and designed the experiments: RJB KRD JLD AC KD PDW LH. Performed the experiments: KRD WW JLD AC AA JK. Analyzed the data: RJB LGJ PDW LH. Contributed reagents/materials/analysis tools: KRD JK PDW. Wrote the paper: RJB LH.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0051545