Abstract
BackgroundHumoral immune responses in human immunodeficiency virus (HIV)-infected and uninfected children with Pneumocystis pneumonia (PcP) are poorly understood. MethodsConsecutive 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. Results149 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. ConclusionsYoung 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.
Highlights
Pneumocystis jirovecii is an opportunistic pulmonary pathogen of worldwide distribution
P. jirovecii remains a major cause of lifethreatening pneumonia in children who are immunocompromised by human immunodeficiency virus (HIV) infection, cancer, or other disorders
The aims of this study were: 1) to characterize the IgG and IgM antibody responses to major surface glycoprotein (MsgC) fragments in HIV-infected and HIV-uninfected children hospitalized with Pneumocystis pneumonia (PcP) (PcP+) and other causes of pneumonia (PcP-); 2) to identify specific host factors that are independent predictors of these antibody levels; 3) to determine if any of the antibody responses are independent predictors of mortality from PcP
Summary
Pneumocystis jirovecii is an opportunistic pulmonary pathogen of worldwide distribution. 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% [7,8,9,10,11]. Humoral immune responses in human immunodeficiency virus (HIV)-infected and uninfected children with Pneumocystis pneumonia (PcP) are poorly understood
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