Date Published: July 10, 2017
Publisher: Public Library of Science
Author(s): Robert J. Blount, Kieran R. Daly, Serena Fong, Emily Chang, Katherine Grieco, Meredith Greene, Stephen Stone, John Balmes, Robert F. Miller, Peter D. Walzer, Laurence Huang, Lynn M Schnapp.
Humoral immunity plays an important role against Pneumocystis jirovecii infection, yet clinical and environmental factors that impact bronchoalveolar antibody responses to P. jirovecii remain uncertain.
From October 2008—December 2011 we enrolled consecutive HIV-infected adults admitted to San Francisco General Hospital (SFGH) who underwent bronchoscopy for suspected Pneumocystis pneumonia (PCP). We used local air quality monitoring data to assign ozone, nitrogen dioxide, and fine particulate matter exposures within 14 days prior to hospital admission. We quantified serum and bronchoalveolar lavage fluid (BALF) antibody responses to P. jirovecii major surface glycoprotein (Msg) recombinant constructs using ELISA. We then fit linear regression models to determine whether PCP and ambient air pollutants were associated with bronchoalveolar antibody responses to Msg.
Of 81 HIV-infected patients enrolled, 47 (58%) were diagnosed with current PCP and 9 (11%) had a prior history of PCP. The median CD4+ count was 51 cells/μl (IQR 15–129) and 44% were current smokers. Serum antibody responses to Msg were statistically significantly predictive of BALF antibody responses, with the exception of IgG responses to MsgC8 and MsgC9. Prior PCP was associated with increased BALF IgA responses to Msg and current PCP was associated with decreased IgA responses. For instance, among patients without current PCP, those with prior PCP had a median 73.2 U (IQR 19.2–169) IgA response to MsgC1 compared to a 5.00 U (3.52–12.6) response among those without prior PCP. Additionally, current PCP predicted a 22.5 U (95%CI -39.2, -5.82) lower IgA response to MsgC1. Ambient ozone within the two weeks prior to hospital admission was associated with decreased BALF IgA responses to Msg while nitrogen dioxide was associated with increased IgA responses.
PCP and ambient air pollutants were associated with BALF IgA responses to P. jirovecii in HIV-infected patients evaluated for suspected PCP.
Pneumocystis pneumonia (PCP), a disease first clinically described in premature and malnourished children in the 1940s  and later found to be an important opportunistic infection among immunosuppressed patients such as those with HIV infection, continues to impart significant morbidity and mortality worldwide .
In this prospective cohort study we investigated clinical and environmental influences on bronchoalveolar antibody responses to P. jirovecii Msg constructs. We found that serum antibody responses to Msg were predictive of bronchoalveolar responses, and that although most patients had BALF IgA responses to Msg, the majority did not have detectable BALF IgM or IgG responses. PCP was significantly associated with BALF IgA responses to Msg such that those with a prior history of PCP (and not current PCP) had elevated IgA responses and those with a current diagnosis of PCP had reduced IgA responses. Pre-admission ambient levels of O3 were associated with decreased IgA responses while NO2 was associated with increased BALF IgA responses to Msg.
Prior studies have shown that humoral immunity plays an important role in host defense against P. jirovecii. In our study we found that both clinical and environmental factors were associated with BALF IgA responses to Pneumocystis Msg. IgA was increased in those with a prior history of PCP yet decreased in those with current PCP, findings suggestive of immunologic memory and possible airway consumption during active infection, though small numbers in these subgroups limit the generalizability of these findings. Ozone levels within the two weeks prior to hospital admission were associated with decreasing trends of IgA responses to Msg, while NO2 levels were associated with increasing trends of IgA to Msg. Although air pollutant and BALF IgA responses to Msg were not associated with clinical outcomes in this prospective cohort, the sample size was small and air pollutant levels low, and further studies are needed to evaluate the clinical significance of environmental influences on lung immunity against P. jirovecii.