Systems approach to uncover signaling networks in primary immunodeficiency diseases

Abstract

This broad, unbiased approach of studying signaling across all circulating immune cells in healthy subjects allowed identification of disrupted signaling networks in patients with primary immunodeficiencies.

Conflict of interest statement

Competing interests: All authors declare no conflicting financial interest related to this study.

Figures

Fig.1. Signaling responses of immune cell subtypes to canonical stimuli

Fold changes of phospho signaling proteins after stimulation compared to baseline across nine pathways, shown according to stimuli and cell subtype. All responses were measured 15 minutes after stimulation. This signaling map compiled from five healthy subjects provides comprehensive view of well-established, recently described, and previously undescribed signaling changes.

Fig. 2. Defects in baseline signals and responses to signals in PI disease

Baseline phosphorylation levels of subjects with (A) GOF STAT1 and (B) STAT3 deficiency that are greater than 1.5 fold or less than 0.75 fold of corresponding baseline phosphorylation levels in controls. Signaling fold changes in (C) GOF STAT1 and (D) STAT3 deficiency subjects that fall outside of the 95% CI of corresponding fold changes in controls (indicated by boxes) with p value of <0.05 are shown. Unstimulated points are scaled to the unstimulated value for the subject with GOF STAT1 (C) or STAT3 deficiency (D) or the average for the five healthy subjects. Stimulation responses are shown for the PID subjects (purple or green circle) and the healthy controls (grey circles). Stimuli and signals are across the top, and cell type is across the side. Only the responses that are statistically significant are shown.