Could we discuss the molecular signature of immune dysregulation?

Abstract Introduction Immune dysregulation (ID), defined as aberrant immune activation or suppression, may result in autoimmune or inflammatory disorders, lymphoproliferative malignancies, and allergic diseases. Apoptosis, nuclear factor-κB (NFκB), and phosphoinositide 3-kinase (PI3K) pathways are major pathways involved in ID. Objective This study aimed to assess ID using targeted inflammatory gene-expression profiles in comparison with controls. Methods We grouped patients according to presenting features: autoimmune lymphoproliferative syndrome (ALPS) (group 1), immune cytopenia (group 2), and EBV-associated lymphoproliferation (group 3). We established real-time quantitative polymerase chain reaction (RT-qPCR) analysis for selected genes (CASP8, CASP10, FAS, FASL, AKT, MAP3K7, MAP3K14, mTOR, NFKB1, NFKB2, NFKBIA, and TRAF3) involved in inflammatory pathways, and calculated gene expression fold changes using the logarithmic Delta-Delta Ct (2^(–delta delta CT)) method. Results The median age of symptom onset in group 1 (n=10), group 2 (n=12), and group 3 (n=10) was 9.3 (0.5-38.7), 5.7 (0.7-19), 22.5 (0.7-45) years, respectively (p=0.181). The median age at hospital admission was 12 (1.9-38.7), 9.4 (2.3-35), and 34.8 (0.9-54.7) years in groups 1, 2, and 3, respectively (p=0.152). There was a significant difference between patient and control groups (p<0.05), but none among patient groups regarding targeted gene expression (relative quantification values). According to ROC curve analysis, the most discriminative target genes are NFKB2, MAP3K7, AKT, mTOR, NFKB1, and FAS. Conclusion We propose an ID signature that includes targeted gene expression profiles (NFKB1, NFKB2, MAP3K7, AKT, mTOR, and FAS) and suggest using these specific gene expressions as a biomarker for diagnosis and therapy response in ID.