Table 2. Gene Set Analysis – selected pathway results illustrate a strong downward regulation of the adaptive immune response across multiple pathways for all disease groups versus healthy controls regardless of patient diagnosis.

GeneSet	Annotation	IPAH_v_Control	SSc-PH-ILD_v_Control	SSc-PAH_v_Control	SSc_v_Control
TOB1 PATHWAY	BioCarta	−4.620	−4.205	−5.096	−6.653
CA2+NFAT SIGNALING	GEArray	−5.695	−3.866	−5.047	−5.395
IL12 PATHWAY	BioCarta	−3.757	−3.740	−4.826	−6.919
TCR PATHWAY	BioCarta	−4.963	−4.673	−5.085	−4.813
CCR5 PATHWAY	BioCarta	−4.488	−3.189	−5.027	−5.916
ARE/NRF2 PATHWAY	BioCarta	−4.174	−2.190	−4.210	−5.027
IL2PATHWAY	BioCarta	−3.685	−3.575	−2.811	−3.572
TH1-TH2-TH3 GENES	SABiosciences	−3.263	−3.289	−1.938	−4.736

Enrichment scores are derived using the PAGE technique (see Methods) and are equivalent to (gene set size adjusted) Gaussian distributed z scores. The negative sign direction of the scores indicates that for each of the indicated pathways and comparisons the average gene expression is lower in the disease group than in controls. Shaded pathways (Ca2+NFAT signaling and the TCR Pathway) are broken out on a gene by gene and sample by sample basis in Figure 2.