Serologic responses to pneumocystis proteins in HIV patients with and without Pneumocystis jirovecii pneumonia

Abstract

Background: Immune responses to Pneumocystis jirovecii are not well understood in HIV infection, but antibody responses to proteins may be useful as a marker of Pneumocystis risk or presence of Pneumocystis pneumonia (PcP).

Design: Retrospective analysis of a prospective cohort.

Methods: Enzyme-linked immunosorbent assays of antibodies to recombinant Pneumocystis proteins of major surface glycoprotein fragments (MsgC1, C3, C8, and C9) and of antibody titers to recombinant kexin protein (KEX1) were performed on 3 sequential serum samples up to 18 months before and 3 samples after first AIDS-defining illness from Multicenter AIDS Cohort Study participants and compared between those who had PcP or a non-PcP AIDS-defining illness.

Results: Fifty-four participants had PcP and 47 had a non-PcP AIDS-defining illness. IgG levels to MsgC fragments were similar between groups before first AIDS-defining illness, but the PcP group had higher levels of IgG to MsgC9 (median units/mL 50.2 vs. 22.2, P = 0.047) post-illness. Participants with PcP were more likely to have an increase in MsgC3 [odds ratio (OR): 3.9, P = 0.02], MsgC8 (OR: 5.5, P = 0.001), and MsgC9 (OR: 4.0, P = 0.007). The PcP group was more likely to have low KEX1 IgG before development of PcP (OR: 3.6, P = 0.048) independent of CD4 cell count and to have an increase in high IgG titers to KEX1 after PcP.

Conclusions: HIV-infected individuals develop immune responses to both Msg and kexin proteins after PcP. Low KEX1 IgG titers may be a novel marker of future PcP risk before CD4 cell count has declined below 200 cells per microliter.

Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest.

Figures

Figure 1

Level of antibodies to MsgC segments at visit 3 (Pre) and visit 4 (Post), before and after the first AIDS-defining illness, respectively. Lines and whiskers represent the median value and interquartile range. No PcP = group that had an illness other than PcP for their first AIDS-defining illness. PcP = group that had PcP as their first AIDS-defining illness.

Figure 2

Proportion of subjects in each group who had an increase in antibody level to each MsgC segment after their first AIDS-defining illness (visit 4) of ≥1.5 times the level prior to the first AIDS-defining illness (visit 3). No PcP = group that had an illness other than PcP for their first AIDS-defining illness. PcP = group that had PcP as their first AIDS-defining illness.

Figure 3

A) Proportion of subjects in each group who had a low (≤1:3200) IgG reciprocal endpoint titer to KEX1 at each visit. Visits 1, 2, and 3 are prior to the first AIDS-defining illness, and visits 4, 5, and 6 are after the first AIDS-defining illness. B) Proportion of subjects in each group who had a high (>1:3200) IgG antibody titer to KEX1 before (Visit 1) and after (Visit 6) AIDS-defining illness. No PcP = group that had an illness other than PcP for their first AIDS-defining illness. PcP = group that had PcP as their first AIDS-defining illness.