Variants in immune-regulatory loci that recur in international studies—IRAK1, TNFAIP3, IL6R/IL6ST, and transcriptional regulators such as AFF3 and IKZF3—in our patients are supported by the central role of NF-κB and IL-6 signalling in SSc pathogenesis [37,48]. Here, NFKB1 is linked to systemic sclerosis.