Pneumocystis pneumonia and rheumatic disease: diagnostic potential of circulating microbial cell-free DNA sequencing
Abstract Objectives This study aimed to explore the clinical utility of circulating microbial cell-free DNA (cfDNA) sequencing as a non-invasive approach for diagnosing Pneumocystis jirovecii pneumonia (PJP) in immunocompromised patients with rheumatic disease (RD). Methods The study included 72 RD patients with suspected lung infections admitted to Renji hospital. Eighteen individuals were diagnosed with PJP, and 54 patients without PJP were enrolled as control group. All patients had undergone pulmonary computed tomography scans, and blood and respiratory tract specimens had been subjected to metagenomic next-generation sequencing (mNGS) and conventional microbiological tests. The clinical and laboratory parameters were collected and efficacy of circulating microbial cfDNA of PJP was evaluated. Results Of the 18 patients with PJP, the average age was 53.0 years and the median time between RD diagnosis and PJP presentation was 126 days (IQR 84.0–176.3). Low circulating CD4+ cell counts and a lack of PJP prophylaxis were observed in the patients. Metagenomic NGS of circulating microbial cfDNA was performed in 69 patients including 15 cases with PJP and 54 controls. Twelve (80%) of 15 analysed blood samples contained Pneumocystis jirovecii (PJ) sequences in PJP group with PJ not detected among controls. There was a significant difference between PJP and non-PJP groups (p < 0.001) with a sensitivity of 83.3% and specificity of 100% when using plasma cfDNA sequencing. Higher β-D-glucan levels were found in patients with positive results for PJ in plasma cfDNA sequencing. Conclusion Metagenomic NGS of circulating microbial cfDNA is a potential tool for diagnosing PJP in RD patients.