Investigating Pathogen Infections in Patients With Primary ITP

In a study published in Experimental Hematology & Oncology, researchers used metagenomic sequencing to examine plasma pathogens undetectable with conventional technologies in patients with immune thrombocytopenia (ITP).

The authors found that impaired mitochondria function in regulatory T cells (Tregs) appeared to decrease oxidative phosphorylation (OXPHOS)-derived adenosine 5′-triphosphate (ATP) and overall metabolism flux in patients with ITP, which they suggested could be the cause of steroid resistance in those patients.

The study enrolled 75 patients with a new diagnosis of primary ITP. Researchers used metagenomic next-generation sequencing (mNGS) and liquid chromatography-mass spectrometry to evaluate participants’ pathogens and plasma lipids, respectively. Flow cytometry was used to evaluate CD4 T cells, CD8 T cells, mitochondrial reactive oxygen species, and mitochondrial membrane potential. Cellular metabolism changes were assessed with a real-time ATP rate assay (Seahorse XF).

Pathogen Infections Correlate With ITP Treatment Outcomes

The investigators detected positive plasma pathogens in 7 patients, of which 5 (71.4%) did not respond to first-line treatment with corticosteroids. Patients with pathogen-positive ITP had significantly increased Tregs and a significantly decreased Treg ATP rate index compared with pathogen-negative patients and healthy controls.

Furthermore, compared with controls, patients with pathogen-positive ITP had decreased overall metabolism flux (P=.004), a higher proportion of glycolysis-derived ATP, and a lower proportion of OXPHOS-derived ATP in Tregs. Lastly, the authors noted that mitochondrial membrane potential for T-helper 17 cells and Tregs were decreased in patients with pathogen-positive or pathogen-negative ITP compared with controls (all P<.05).

Ultimately, the authors proposed that using mNGS to identify potential subclinical pathogen infections would be helpful for optimizing treatment in patients with ITP who do not adequately respond to first-line treatment with corticosteroids.

Related: Identifying Biomarkers for Diagnosing Immune Thrombocytopenia