Figure 2.

Whole blood transcriptional profile of the patient with Blau syndrome compared to controls. A, Expression values of transcripts from 1 time point pretreatment and 1, 2, 3, 4, and 5 months after initiation of canakinumab therapy (V1–5) were log₂ transformed and normalized to the median value in 4 healthy controls. Fold change analysis of the sample from the untreated patient with Blau syndrome and 4 healthy controls resulted in 1,993 differentially expressed transcripts. Hierarchical clustering of these probes was generated using the Pearson correlation method. B, Modular analysis of samples from the patient with Blau syndrome was performed. The results revealed up-regulation of neutrophil and inflammation modules and down-regulation of adaptive immune responses. A t-test was performed for each (baseline and followup) time point and for the healthy controls, with an assumption of equal variance in an error model. Each column corresponds to 1 time point. Within each module, numbers of significant genes were identified and their percentage represented as up-regulated or down-regulated. The transcript composition for each module has been described elsewhere (9). DC = dendritic cell; NK = natural killer. In A and B, red signifies up-regulation and blue signifies down-regulation. C, In the sample from the untreated patient with Blau syndrome, 496 up-regulated transcripts were analyzed by IPA. An inflammatory response network centered around Toll-like receptor 2, inflammasome components, interleukin-1/interleukin-18 signaling, and neutrophil-encoded transcripts was predominant.