Dataset with samples from Individuals with defects in Intrinsic and Innate Immunity:

1)- Herpes simplex encephalitis (HSE):

- TLR3 deficiency, Phenotype OMIM number 6130023

- TBK1 deficiency, Phenotype OMIM number Not yet assigned

2)- Predisposition to severe viral infection:

- STAT1 deficiency, Phenotype OMIM number 613796

see PID classification: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4659841/

We report here two unrelated HSE patients carrying different heterozygous mutations (D50A and G159A) in TBK1, the gene encoding TANK-binding kinase 1, a kinase at the crossroads of multiple IFN-inducing signaling pathways. Both mutant TBK1 alleles are loss-of-function, but through different mechanisms: protein instability (D50A) or a loss of kinase activity (G159A). Both are also associated with an autosomal dominant (AD) trait, but by different mechanisms: haplotype-insufficiency (D50A) or negative dominance (G159A). A defect in poly(I:C)-induced TLR3 responses can be detected in fibroblasts heterozygous for G159A, but not for D50A TBK1.

Skin fibroblast cell lines were derived from healthy controls (n=3), patients with deficiencies for TBK1 (n=2), TLR3 (n=2), STAT1 (n=1) and cultured for 2 or 8 hours in the presence of IFNa (105 IU/ml), IL1b (20ng/ml), or poly I:C (25ug/ml) or left unstimulated for the same length of time.