Patients with APECED possess altered NFkB pathway gene expression.
APECED, or autoimmune polyendocrinopathy candidiasis ectodermal dystrophy, is an autoimmune disorder caused by mutations in the autoimmune regulator gene AIRE (1, 2). Though it is known that 42 separate mutations in the AIRE gene can cause APECED (3), it not understood how these mutations lead to the pathology seen in APECED patients, and there are limited systems-level studies of the underlying transcriptional behavior of the immune cells of patients with APECED (4). In this study, we used a dataset (5) to compare the transcriptomes of monocyte-derived dendritic cells (moDCs) from patients with APECED and from control, non-affected patients in order to understand and describe the basic transcriptional nature of cells from patients with APECED. We found that four separate components of the NF-kB signaling pathway were among the genes most differentially expressed by moDCs from APECED patients. These included the NF-kB subunit REL, the NF-kB inhibitor alpha NFKBIA, the NF-kB inhibitor beta NFKBIZ, and the NF-kB inhibitor interacting Ras like 2 gene NKIRAS2. This is the first systems-level analysis of moDCs from patients with APECED to document perturbed gene expression in the NF-kB signaling pathway.