Cellular signatures of immune dysregulation in inborn errors of immunity: development of a quantitative immune balance score - PubMed
4 hours ago
- #inborn errors of immunity
- #biomarker
- #immune dysregulation
- Study focuses on immune dysregulation in inborn errors of immunity (IEIs), particularly primary immune regulatory disorders (PIRDs).
- A quantitative immune balance score (IDS) was developed to measure inflammatory/regulatory imbalance using multiparametric flow cytometry and computational modeling.
- Patients showed significant immune network alterations, including reduced FOXP3+ Tregs and transitional Breg cells, and expanded BCL6+, CD4+ ICOS+BCL6+ Tfh-like subsets.
- IDS distinguished patients from controls (AUC = 0.75) and correlated inversely with clinical z scores (r = -0.65).
- Subgroup analyses revealed elevated IDS in genetically confirmed PIRDs, while non-PIRDs had IDS values similar to controls.
- IDS combined with clinical features stratified patients into three clusters aligned with genetic causes.
- Machine-learning models improved stratification of mild and moderate cases, but severe phenotypes remained heterogeneous.
- IDS is proposed as a novel biomarker for immune dysregulation, aiding patient stratification and guiding therapeutic interventions.