Panel a contains multiple line
graphs showing the relative expression of various genes (ISG15, IFI44L,
IFIT1, IFI27, RSAD2, SIGLEC1, IFNB1, TNF, IL6, IL1B) relative to ACTB in
different individuals (Proband pre-treatment, Proband post-treatment,
Paternal, Maternal, Healthy Donors). The x-axis represents different genes,
and the y-axis represents relative expression levels. The graphs show a
significant reduction in expression of Interferon-stimulated genes
post-treatment. Panel b contains two line graphs tracking the proband's
stature and weight from 13.2 years old to 16 years old. The x-axis
represents age in years, and the y-axis represents stature in centimeters
and weight in kilograms. The graphs show the proband's growth
percentiles before and after tofacitinib treatment as indicated by a green
line. Panel c contains two sets of photographs of the proband before and
after tofacitinib treatment, showing improvements in lesions under the eyes
and perniosis of the toes.
Tofacitinib reduced transcriptional IFN signature and led to symptom improvement. (a) 6-gene transcriptional IFN-I score performed on RNA from PBMCs taken from the indicated individuals (geometric mean). Genes included in the signature were measured by qPCR, and expression is plotted relative to ACTB for ISG15, IFI44L, IFIT1, IFI27, RSAD2, and SIGLEC1. Measurement of IFNB1 and other non-IFN cytokine transcripts (TNF, IL6, and IL1B) was also performed (mean, pink line represents change in transcription from separate PBMC RNA samples taken from the proband before and after tofacitinib therapy; GOI, gene of interest; ND, not detected). (b) Growth charts tracking stature (left) or weight (right) of the proband (pink line) from 13.4 to 15.8 years old. Commencement of tofacitinib (green line) is indicated. Percentiles from the Centre for Disease Control are depicted by the grey shaded area. (c) Photographs of the proband before (left) and after (right) tofacitinib treatment. Lesions under the eyes and perniosis of the toes have improved with treatment.