Humoral Immune Responses to Pneumocystis jirovecii Antigens in HIV-Infected and Uninfected Young Children with Pneumocystis Pneumonia
Walzer PD (2013) Humoral Immune Responses to Pneumocystis jirovecii Antigens in HIV-Infected and
Uninfected Young Children with Pneumocystis Pneumonia. PLoS ONE 8(12): e82783. doi:10.1371/journal.pone.0082783
Humoral Immune Responses to Pneumocystis jirovecii Antigens in HIV-Infected and Uninfected Young Children with Pneumocystis Pneumonia
Kpandja Djawe 0
Kieran R. Daly 0
Linda Levin 0
Heather J. Zar 0
Peter D. Walzer 0
Marta Feldmesser, Albert Einstein College of Medicine, United States of America
0 1 Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America, 2 Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America, 3 Research Service, Veterans Affairs Medical Center , Cincinnati , Ohio, United States of America, 4 Department of Pediatrics and Child Health, University of Cape Town , Cape Town , South Africa
Background: Humoral immune responses in human immunodeficiency virus (HIV)-infected and uninfected children with Pneumocystis pneumonia (PcP) are poorly understood. Methods: Consecutive children hospitalized with acute pneumonia, tachypnea, and hypoxia in South Africa were investigated for PcP, which was diagnosed by real-time polymerase chain reaction on lower respiratory tract specimens. Serum antibody responses to recombinant fragments of the carboxyl terminus of Pneumocystis jirovecii major surface glycoprotein (MsgC) were analyzed. Results: 149 children were enrolled of whom 96 (64%) were HIV-infected. PcP occurred in 69 (72%) of HIV-infected and 14 (26%) of HIV-uninfected children. HIV-infected children with PcP had significantly decreased IgG antibodies to MsgC compared to HIV-infected patients without PcP, but had similar IgM antibodies. In contrast, HIV-uninfected children with PcP showed no change in IgG antibodies to MsgC, but had significantly increased IgM antibodies compared to HIV-uninfected children without PCP. Age was an independent predictor of high IgG antibodies, whereas PcP was a predictor of low IgG antibodies and high IgM antibodies. IgG and IgM antibody levels to the most closely related MsgC fragments were predictors of survival from PcP. Conclusions: Young HIV-infected children with PcP have significantly impaired humoral immune responses to MsgC, whereas HIV-uninfected children with PcP can develop active humoral immune responses. The children also exhibit a complex relationship between specific host factors and antibody levels to MsgC fragments that may be related to survival from PcP.
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Funding: This work was supported by the National Institutes of Health Grant R01 HL090335 and the Department of Veterans Affairs, the National
Research Foundation, South Africa; an ASTRA-Zeneca Respiratory Award from the South African Thoracic Society and the Medical Research Council of
South Africa. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: ASTRA-Zeneca gave a research grant to the South African Thoracic Society (SATS) and the grant was administered by SATS.
ASTRA-Zeneca had nothing how SATS administered the grant or spent the money. ASTRA-Zeneca had nothing to do with any other relevant declarations
relating to employment, consultancy, patents, products in development, or marketed products etc). We also confirm that this grant does not alter our
adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in our guide for authors.
These authors contributed equally to this work.
Pneumocystis jirovecii is an opportunistic pulmonary
pathogen of worldwide distribution. Primary P. jirovecii infection
is acquired during the first few months of life, and is either
asymptomatic or a self-limited infection [1,2].
Seroepidemiological studies have shown that by 2-3 years of
age, most healthy children have been infected with the
organism [2-6]. P. jirovecii remains a major cause of
lifethreatening pneumonia (termed PcP) in children who are
immunocompromised by human immunodeficiency virus (HIV)
infection, cancer, or other disorders. This is especially true in
children in low or middle income countries where the disease
occurs in 10% to 49% of HIV-infected children hospitalized for
pneumonia with an in-hospital mortality rate of 20% to 63%
[7-11].
The diagnosis of PcP has traditionally been made by the
demonstration of the organism by histologic or
immunofluorescent staining in specimens that have been
carefully obtained from the respiratory tract. It is likely that this
method underestimates the true incidence of PcP, particularly
in areas with limited laboratory facilities [1-14]. Recent studies
in adults with and without PcP have shown that the polymerase
chain reaction (PCR), particularly real time (RT)-PCR, is more
sensitive than microscopy in detecting P. jirovecii and may also
distinguish colonization from active disease [15 (...truncated)