Human Immunodeficiency Virus-Infected Patients with Prior<i>Pneumocystis</i>Pneumonia Exhibit Increased Serologic Reactivity to Several Major Surface Glycoprotein Clones

Daly, Kieran R.; Koch, Judy; Shire, Norah J.; Levin, Linda; Walzer, Peter D.

doi:10.1128/cvi.00140-06

Cited by 20 publications

(55 citation statements)

References 55 publications

(48 reference statements)

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“…In a series of studies utilizing recombinant Msg fragments that cover the entire protein-coding region, Walzer and colleagues developed an enzymelinked immunosorbent assay (ELISA) that has shown promise in diagnostic testing and epidemiologic studies (53,54,312). Of particular interest is a fragment that encodes the relatively conserved carboxy-terminal region of the protein (MsgC) (46,(53)(54)(55)67). HIV-infected patients with active PCP have significantly higher antibody titers to MsgC than patients with pneumonia due to other causes (68).…”

Section: Pneumocystis Antigensmentioning

confidence: 99%

Colonization by Pneumocystis jirovecii and Its Role in Disease

2012

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SUMMARY Although the incidence of Pneumocystis pneumonia (PCP) has decreased since the introduction of combination antiretroviral therapy, it remains an important cause of disease in both HIV-infected and non-HIV-infected immunosuppressed populations. The epidemiology of PCP has shifted over the course of the HIV epidemic both from changes in HIV and PCP treatment and prevention and from changes in critical care medicine. Although less common in non-HIV-infected immunosuppressed patients, PCP is now more frequently seen due to the increasing numbers of organ transplants and development of novel immunotherapies. New diagnostic and treatment modalities are under investigation. The immune response is critical in preventing this disease but also results in lung damage, and future work may offer potential areas for vaccine development or immunomodulatory therapy. Colonization with Pneumocystis is an area of increasing clinical and research interest and may be important in development of lung diseases such as chronic obstructive pulmonary disease. In this review, we discuss current clinical and research topics in the study of Pneumocystis and highlight areas for future research.

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Section: Pneumocystis Antigensmentioning

confidence: 99%

Colonization by Pneumocystis jirovecii and Its Role in Disease

2012

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“…Our findings suggest that hazardous alcohol use and IDU may be important cofactors to consider in assessing P. jirovecii antibody responses and colonization. In addition, prior studies have found that episodes of PCP are associated with greater P. jirovecii antibody responses (10). More severely impaired lung function in COPD patients has been associated with undetectable serum antibodies to Kexin, another P. jirovecii antigen (28).…”

Section: Discussionmentioning

confidence: 99%

“…Quantitative P. jirovecii IgG antibody responses were measured using an enzyme-linked immunosorbent assay (ELISA) as previously described (6,10,39). Serum specimens to be analyzed and the standard reference serum were tested against four recombinant MsgC fragments (MsgC1, MsgC3, MsgC8, and MsgC9); phosphate-buffered saline (PBS) without antigen was used as a negative control.…”

Section: Methodsmentioning

confidence: 99%

“…We then developed three variants (MsgC3, MsgC8, and MsgC9) of MsgC1 and used them to better define the reactivity to this fragment. These clones exhibit 77% to 99% homology at the amino acid level (10) and are useful in studying antibody responses in different geographic locations. Although the factors associated with the magnitude of the antibody response remain incompletely understood, our studies thus far have demonstrated that prior PCP, age, geography, and failure to take PCP prophylaxis are associated with high serum P. jirovecii antibody levels in HIV-infected patients (6,10,39).…”

mentioning

confidence: 99%

“…Although serologic studies of P. jirovecii infection have previously been hampered by the lack of suitable reagents, the use of recombinant P. jirovecii antigens such as the major surface glycoprotein (Msg) and Kexin, another P. jirovecii antigen, has shown promise in measuring P. jirovecii antibodies in humans (7,8,9,10,20,28). Msg is encoded by a multigene family and is capable of antigenic variation.…”

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confidence: 99%

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Decreased Serum Antibody Responses to Recombinant Pneumocystis Antigens in HIV-Infected and Uninfected Current Smokers

Crothers

Daly

Rimland

et al. 2011

Clin Vaccine Immunol

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Serologic studies can provide important insights into the epidemiology and transmission of Pneumocystis jirovecii. Exposure to P. jirovecii can be assessed by serum antibody responses to recombinant antigens from the major surface glycoprotein (MsgC), although factors that influence the magnitude of the antibody response are incompletely understood. We determined the magnitudes of antibody responses to P. jirovecii in comparison to adenovirus and respiratory syncytial virus (RSV) in HIV-infected and uninfected patients and identified predictors associated with the magnitude of the response. We performed a cross-sectional analysis using serum samples and data from 153 HIV-positive and 92 HIV-negative subjects enrolled in a feasibility study of the Veterans Aging Cohort 5 Site Study (VACS 5). Antibodies were measured using an enzyme-linked immunosorbent assay (ELISA). Independent predictors of antibody responses were determined using multivariate Tobit regression models. The results showed that serum antibody responses to P. jirovecii MsgC fragments were significantly and independently decreased in current smokers. Antibodies to P. jirovecii also tended to be lower with chronic obstructive pulmonary disease (COPD), hazardous alcohol use, injection drug use, and HIV infection, although these results were not statistically significant. These results were specific to P. jirovecii and did not correlate with adenovirus. Antibody responses to RSV were in the inverse direction. Thus, current smoking was independently associated with decreased P. jirovecii antibody responses. Whether smoking exerts an immunosuppressive effect that affects the P. jirovecii antibody response, colonization, or subsequent risk for disease is unclear; prospective, longitudinal studies are needed to evaluate these findings further.

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