PMC8578119_01
(A) Patients' Timeline. (B) Brain MRI. Brain MRI, axial T2-weighted image at the age of 18 months (A), 36 months (B), 40 months (C), 5 years (D). Putamen (black arrow) and head of caudate nucleus (white asterisk), show normal signal at 18 months (A); follow-up MRIs (B,C) show progressively increasing diffuse hyperintensity in both gray matter nuclei with volume loss of the putamina, consistent with bilateral striatal necrosis; after 18 months of therapy with Ruxolitinib the MRI (D) showed no progression of the basal ganglia abnormality.
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F1
The same genotype was originally observed in the older brother who was born 6 years before from an uneventful pregnancy and delivery (see Figure 1A). Neuroimaging study of the child at that age by MRI was also normal (Figure 1A). Re-evaluation of the child at 40 months of age, failed to demonstrate clinical signs of improvement and on MRI there was a slight increase of the signal abnormality in both striatal nuclei (Figure 1C), which prompted us to taper prednisone and start treatment with a JAK-inhibitor, in an attempt to prevent disease progression. Neuroimaging assessment after 18 months of ruxolitinib therapy by MRI showed no change of the signal intensity abnormality in the basal ganglia (Figures 1A,D).
Trend of interferon-signaling gene expression score from June 2018 to August 2020. (A) IFN score P#1 pre-therapy, not available measurement of P#2. (B) IFN score during treatment of P#1, in parallel with P#2, and report of simultaneous respiratory infections. P#1 shows mild increment of IFN score during infections, while P#2 presents significant increments. Also, during infection free periods, there is discrepancy of the values. The interferon score was calculated as the median fold changes of expression of a panel of interferon-stimulated genes (ISGs: IFI27, IFI44L, IFIT1, RSAD2, ISG15, and SIGLEC1). The gene expression was analyzed by quantitative reverse transcription polymerase chain reaction (qPCR) using 18s as gene housekeeping to normalize the results. Relative quantification (RQ) was calculated with the formula 2-DeltaDeltaCt, using as calibrator a pool of 17 healthy controls. The mean interferon score of the healthy donors plus two standard deviations above the mean was calculated. Scores higher than this value (4.67) were designated as positive.
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F2
IS showed lower values when compared with measurements performed before starting ruxolitinib treatment (see Figure 2).