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Host response proteins, fungal antigens identify invasive Aspergillus in leukemia patients
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A biomarker panel candidate of host response proteins and the fungal antigen galactomannan improved the detection of invasive pulmonary aspergillosis in leukemia patients, according to recent findings.
“Invasive pulmonary aspergillosis (IPA) is an opportunistic fungal infection in patients undergoing chemotherapy for hematological malignancy, hematopoietic stem cell transplant (HSCT), or other forms of immunosuppression,” Allan R. Brasier, MD, director of the Institute for Translational Sciences at the University of Texas Medical Branch in Galveston, Texas, and colleagues wrote. “In this group, Aspergillus infections account for the majority of deaths due to mold pathogens. Although early detection is associated with improved outcomes, current diagnostic regimens lack sensitivity and specificity.”
Allan R. Brasier
Specifically, clinical-grade, enzyme-linked immunosorbent assays targeting galactomannan (GM), a polysaccharide produced during fungal growth, and (1, 3)-beta-D-glucan (BG), a component of the fungal cell wall, are susceptible to false results, according to the researchers.
To improve detection, potential biomarkers of invasive Aspergillus were evaluated in 46 patients with leukemia and 22 patients with other underlying diseases, including lung and HSCT recipients.
The researchers used 2D gel electrophoresis to assess protein content in plasma samples from patients with proven or probable IPA (n = 61) and matched controls (n = 17). Sixty-six differentially abundant proteins were identified, and the eight most informative proteins were included in the analysis. In addition, stable isotope dilution-selected reaction monitoring assays detected four peptides that were significantly different between IPA cases and controls.
Further analysis revealed eight plasma proteins, four peptides and fungal antigens reproducibly differed between cases and controls in patients with leukemia but not in lung transplants and stem cell transplants, suggesting “informative host response biomarkers of IPA may be highly dependent on the primary underlying disease state,” Brasier and colleagues wrote.
The biomarker panel candidate was verified in an independent cohort of 57 patients with leukemia as their primary underlying disease. Both fungal antigens as well as host proteins leucine-rich globulin, fibrinogen-A and alpha antitrypsin, and three APOA2 peptides were consistently different in cases vs. controls.
Brasier and colleagues assessed several combinations of proteins and determined that GM combined with host response proteins yielded the highest diagnostic accuracy.
“We note that BG produces poor performance classifiers in much the same manner as those by GM, and in combination, a classifier built with both GM and BG does not produce a robust classifier for predicting independent test data,” Brasier and colleagues wrote. “By contrast, classification performance of a panel including these two fungal antigens and host response markers provide greater diagnostic power for leukemic IPA than either host response or fungal antigens alone.” – by Stephanie Viguers
Disclosures: The researchers report receiving funds from the NIH.
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