For instance, selected members of the CD40 signaling pathway (e.g., CD40, TRAF1, and NFKB2), and other genes related to B-cell response (e.g., CD70, ICAM1 (CD54), CCL17) were specifically hypermethylated and downregulated in activated memory B cells in the CVID twin (Fig. 4f). Here, CD40 is linked to common variable immunodeficiency.