Serum Antibody Levels to the Pneumocystis jirovecii Major Surface Glycoprotein in the Diagnosis of P. jirovecii Pneumonia in HIV+ Patients

Abstract

Background Pneumocystis jirovecii remains an important cause of fatal pneumonia (Pneumocystis pneumonia or PcP) in HIV+ patients and other immunocompromised hosts. Despite many previous attempts, a clinically useful serologic test for P. jirovecii infection has never been developed.Methods/Principal FindingsWe analyzed serum antibody responses to the P. jirovecii major surface glycoprotein recombinant fragment C1 (MsgC1) in 110 HIV+ patients with active PcP (cases) and 63 HIV+ patients with pneumonia due to other causes (controls) by an enzyme-linked immunosorbent assay (ELISA). The cases had significantly higher IgG and IgM antibody levels to MsgC1 than the controls at hospital admission (week 0) and intervals up to at least 1 month thereafter. The sensitivity, specificity and positive predictive value (PPV) of IgG antibody levels increased from 57.2%, 61.7% and 71.5% at week 0 to 63.4%, 100%, and 100%, respectively, at weeks 3–4. The sensitivity, specificity and PPV of IgM antibody levels rose from 59.7%, 61.3%, and 79.3% at week 0 to 74.6%, 73.7%, and 89.8%, respectively, at weeks 3–4. Multivariate analysis revealed that a diagnosis of PcP was the only independent predictor of high IgG and IgM antibody levels to MsgC1. A high LDH level, a nonspecific marker of lung damage, was an independent predictor of low IgG antibody levels to MsgC1.Conclusions/SignificanceThe results suggest that the ELISA shows promise as an aid to the diagnosis of PCP in situations where diagnostic procedures cannot be performed. Further studies in other patient populations are needed to better define the usefulness of this serologic test.

Serological diagnosis of pneumocystosis: production of a synthetic recombinant antigen for immunodetection of Pneumocystis jirovecii

“…In the state of art of serological diagnosis of PcP, different authors have studied the immune response of patients with and without PcP with different fractions of the recombinant protein Msg of P. jirovecii 1617181920212223242526. Although there are an estimated 100 related but unique copies of the MSG gene in the Pneumocystis genome, a greater variability is notice in the amino-terminus of the Msg protein and the most conserved sequences are present at the carboxyl-terminus.…”

“…Alternatively, promising studies using recombinant antigens of P. jirovecii and antibody immunodetection techniques, such as immunoenzymatic or immunoblotting assays, have shown potential application in the diagnosis and epidemiological studies of PcP1617181920212223242526. The Pneumocystis antigen that has received the most attention is the major surface glycoprotein (Msg), which contains shared and species-specific epitopes, elicits humoral and cellular protective immune responses and plays a central role in the interaction of Pneumocystis with its host27.…”

“…The Pneumocystis antigen that has received the most attention is the major surface glycoprotein (Msg), which contains shared and species-specific epitopes, elicits humoral and cellular protective immune responses and plays a central role in the interaction of Pneumocystis with its host27. The carboxyl-terminal domain of the Msg is reported to be highly immunogenic, the most conserved and reactive region of Msg and to contain both B and T cell conserved protective epitopes1618232425. Therefore, recombinant synthetic amino acid sequences, designed to hold more than one reactive region of the Msg, are promising tools that can increase the sensitivity, specificity, the cost-effectiveness and the standardization of serological tests28.…”

Colonization by Pneumocystis jirovecii and Its Role in Disease

“…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). Recent studies have supported the utility of MsgC titers as indicators of acute or recent PCP (102).…”

Recent Advances in the Diagnosis of <I>Pneumocystis</I> Pneumonia

“…HIV-infected patients with PCP elicited greater responses against MsgC than did HIV-infected patients without PCP or with pneumonia due to other causes, and a prior episode of PCP also presented a higher titer of antibodies against MsgC fragments 27,31) . Antibodies against MsgA, MsgB and MsgC were detected in about 84% healthy blood donors, limiting its usefulness in the diagnosis of PCP.…”