Serum IgG responses against Aspergillus proteins before hematopoietic stem cell transplantation or chemotherapy identify patients who develop invasive aspergillosis.

The ability to identify patients at particularly low risk for invasive aspergillosis (IA) would facilitate more efficient targeting of antifungal prophylaxis. We measured baseline serum immunoglobulin responses against 6 purified recombinant Aspergillus fumigatus proteins before hematopoietic stem cell transplantation (HSCT) or chemotherapy in 73 subjects, including 19 patients who subsequently developed proven or probable IA and 54 uninfected controls. We also assessed responses at the time of IA diagnosis and 4 weeks later (acute and convalescent sera, respectively). Baseline IgG responses against enolase, Ahp1, Hsp90, Crf1, and Cdc37 were significantly higher in the patients with IA compared with controls (P < .05). Cutoff concentrations identified by receiver-operating characteristic curve analysis were 67%-84% sensitive and 52%-67% specific. In a population with a 15% likelihood of developing IA, positive and negative predictive values would be 22%-26% and 92%-95%, respectively. Positive IgG responses against Hsp90, Pep2, Crf1, and Cdc37 were specifically associated with early-onset IA (<40 days) rather than late-onset IA (P ≤ .009). Increased IgG concentrations against Hsp90, Pep2, and Crf1 in convalescent sera versus baseline sera were more likely in the patients with IA who survived (P ≤ .01). IgG responses in acute sera were not correlated with outcomes, and IgM and IgA responses did not differ in baseline, acute, or convalescent sera between the patients and controls. In conclusion, baseline IgG responses against Aspergillus proteins may be useful screening tests for patients at low risk for IA. Our data suggest that some patients with IA have significant colonization or ongoing Aspergillus infections before immunosuppression. As such, IA may reflect unique predispositions to infection and/or progression from endogenous sources.