{'fraction_non_alphanumeric': 0.040993071593533485, 'fraction_numerical': 0.027136258660508082, 'mean_word_length': 5.324817518248175, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Type I interferon signature predicts response to JAK inhibition in haploinsufficiency of A20

The anti-inflammatory protein A20, encoded by TNFAIP3 , is a ubiquitin-modifying enzyme that targets proinflammatory molecules, including those upstream of the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Patients with heterozygous loss-of-function TNFAIP3 mutations develop haploinsufficiency of A20 (HA20), a systemic autoinflammatory disease that can cause severe end-organ pathology.1–3 No available medication directly targets NF-κB signalling; thus, treatment decisions are based on clinical experience. Mild cases are treated with disease-modifying antirheumatic drugs, whereas severe cases are treated with systemic corticosteroids and biological agents, including tumour necrosis factor (TNF)-α and IL-1 receptor (IL-1R) blockade.1 2 We report that a type I interferon (IFN) signature, or elevation of IFN-stimulated genes (ISGs), correlates with disease activity and predicts response to janus kinase (JAK) inhibition in HA20.

A cohort of 12 patients with HA20 is followed at the NIH Clinical Center. All patients were diagnosed by Sanger sequencing, and increased NF-κB activity was confirmed with luciferase assay.2 Five patients had disease that was treatment-refractory or caused end-organ pathology. P1 was a 15-year-old female with p.T604Rfs*93 and severe gastrointestinal ulcerations refractory to TNF-α and IL-1R inhibition. P2–P4 were members of the same extended family with p.F224Sfs*4, aged 28, 32 and 61 years. All three had incomplete responses to TNF-α and IL-1R blockade; P2 had retinal vasculopathy and neuroinflammation, whereas P3 had membranous nephropathy. …