Cell-Free DNA Testing in Acute Infections in Chronic Granulomatous Disease

Introduction Chronic granulomatous disease (CGD) is an inborn error in immunity that results in increased infectious susceptibility to serious infections, often from catalase-positive organisms, due to defects in the NADPH oxidase activity. These microbes are difficult to culture and identify. Noninvasive cell-free DNA tests (Karius Test) are culture-free tools to identify microbes causing infections in CGD, but little published experience exists in CGD. Methods We performed a retrospective review of patients with CGD admitted at our institution for acute infection from 2020–2024 and had Karius testing done. Results Six patients were identified to be admitted eight different times for confirmed or strongly presumed infection. A Karius test was done during each of these admissions. Four admissions were for pneumonia, one for liver abscess, one for peri-rectal abscess, and two for lymphadenitis. In every admission, patients had negative fungal, aerobic/anaerobic, and mycobacterial peripheral blood cultures. All four patients with pneumonia had a bronchoscopy with bronchiolar alveolar lavage (BAL), with one patient undergoing a second bronchoscopy with BAL and transbronchial biopsy. This repeat BAL culture, biopsy tissue culture both grew Burkholderia multivorans, but 16s polymerase chain reaction (PCR) was unrevealing. All other BAL cultures were negative. The two patients with lymphadenitis had excisional lymph node biopsy with negative tissue cultures and 16s polymerase chain reaction on the tissue. The patient admitted for a liver abscess had a positive culture with Staphylococcus aureus growing on abscess drainage. This patient also had a positive Karius test showing S. aureus. The remaining seven Karius tests performed were negative. Conclusion Identifying the causative microorganism in acute infections in patients with CGD can be difficult but is imperative for the treatment of infection. Only 25% of our patients with acute infection had an organism identified through classic means. Noninvasive cell-free DNA testing offers an option to overcome limitations of conventional and often invasive cultures. In our cohort, the only patient who resulted in a positive Karius also had positive cultures from liver abscess. There may be limitations in cell-free DNA testing in patients with CGD, but this does need to be studied further.