(A) Pedigree of a Dutch family with four patients affected from 3 generations. (B) Pedigree of a UK sample with 3 patients affected from 3 generations. (C) Pedigree of a UK sample with 3 patients affected from 2 generations. Patients with candidiasis  =  closed black symbols; male patients  =  squares; female patients  =  circles.

(A) PBMC from two healthy controls and two AD-CMC patients were stimulated for two hours with culture medium, IFN-β (500 U/mL), IFN-γ (1 µg/mL), IL-23 (50 ng/mL) or IL-12 (10 ng/mL). Cells were lysed, and total STAT1, phosphorylated STAT1 and actin were assessed by Western blot. Figure is representative of two separate experiments. (B) Increased immunofluorescence of pSTAT1 in IFN-γ-stimulated CD4⁺ cells from AD-CMC patients. Figure is representative of three separate experiments. (C) PBMCs from three controls and two AD-CMC patients were stimulated with culture medium, IFN-β, or IFN-γ for two hours. The transcription of ICAM1 and MCP-1 was measured using RT-PCR. Bars represent means + SEM.

Defective IL-12R (A) and IL-23R (B) pathways in cells isolated from AD-CMC patients. Data represent mean + SEM from 3 healthy controls and 3 AD-CMC patients (P3 and P4 from family #1 and P3 from family 2). (C) Stimulation of the IFN-γ receptor pathway results in increased production of the proinflammatory cytokine TNFα. Data represent mean + SEM from 3 healthy controls and 3 AD-CMC patients. CD4⁺ T cells from healthy controls were transfected with wild-type or mutant STAT1 plasmid. (D) Decreased transcription of STAT4 upon stimulation with IL-1β (10 ng/mL) and IL-23 (50 ng/mL), (E) and decreased transcription of MCP1 upon IL-12 (10 ng/mL) and IL-18 (10 ng/mL) stimulation. (F) The CD4⁺ cells transfected with mutant STAT1 plasmid showed increased transcription of PD-L1 upon stimulation with IFN-γ (1 µg/mL). Data represent mean + SEM from 6 healthy controls from 3 separate experiments.