Biomarkers Pinpoint Invasive Aspergillosis in Lung Transplant Recipients

Several newly identified biomarkers can help distinguish invasive aspergillosis from aspergillus colonization in lung transplant recipients, according to data from a new study presented at the annual meeting of the International Society for Heart and Lung Transplantation.

Aspergillus, a common environmental mold, can cause potentially serious infection or asymptomatic colonization in patients who have significant lung disease or are immunosuppressed, said Aaron Mishkin, MD, associate professor of medicine at the Lewis Katz School of Medicine at Temple University, Philadelphia, who was not involved in the study.

“Determining if the aspergillus that is present is a colonizing organism vs disease is challenging clinically,” Mishkin said. Clinicians currently rely on criteria including a compatible patient, imaging findings, and a laboratory-based diagnostic such as tissue from a biopsy, cultures, polymerase chain reaction (PCR), or fungal antigen detection, said Mishkin. “Fungal antigen detection has variable specificity and sensitivity,” he noted. New biomarkers that look for an immune response could help differentiate between colonization and infection by assessing an immune-mediated inflammatory response, the hallmark of infection, he said.

To tease out potential biomarkers associated with invasive aspergillosis, Christine Ng, MS, a researcher at the University Health Network, Toronto, Ontario, Canada, and colleagues performed RNA sequencing on samples from 14 control lung transplant patients, 34 with aspergillus colonization, and seven with invasive aspergillosis. They identified potential candidate genes in 15 control samples, 17 aspergillus colonization samples, and 15 invasive aspergillosis samples.

Overall, signaling pathway analysis showed robust immune response, T-cell immunity, and leukocyte immunity in patients with invasive aspergillosis. By contrast, patients with aspergillus colonization showed enriched cellular responses (response to stimuli, epithelium development).

In a real-time quantitative PCR analysis, the researchers validated three biomarkers specific to invasive aspergillosis (IRF7, ZBP1, CYP27B1). Biomarkers AKR1C2, FGF10, and VGLL3 demonstrated specificity for aspergillus colonization. Additionally, biomarkers PTGER3, LPAR3, and COL14A1 were significant when aspergillus colonization was compared to controls but not in comparisons between invasive aspergillosis and aspergillus colonization. 

The study findings were limited by the small sample size, and larger studies are needed before they can be implemented in clinical practice, the researchers wrote. However, the results suggest that the new biomarkers reveal distinct host immune patterns and may improve differentiation of aspergillosis from colonization in lung transplant recipients, they concluded.

Clinical Implications and Next Steps

RNA testing can help differentiate colonization vs infection, Mishkin said. “Colonization is not typically treated, whereas infection would be treated with an anti-fungal and, in the case of a transplant recipient, a reduction in immunosuppression,” he said. “In lung transplantation, a delicate equilibrium must be maintained between achieving optimal immunosuppression and minimizing or treating infection. Any tools that can aid in this decision-making have the potential to enhance patient outcomes,” he added.

The current study was limited by the use of data only from a single center, and the broader applicability to additional populations, broader geographic areas, and a larger number of organisms remains unknown, Mishkin said. “This type of assay does have the possibility of applicability to a larger number of fungal and even bacterial species,” he noted.

A version of this article first appeared on Medscape.com.