Inhibition of JAK-STAT pathway corrects salivary gland inflammation and interferon driven immune activation in Sjögren's disease.

Sarthak GuptaEiko YamadaHiroyuki NakamuraPaola PerezThomas Jf PranzatelliKalie DominickShyh-Ing JangMehdi AbedDaniel MartinPeter BurbeloChangYu ZhengBen FrenchIlias AlevizosZohreh KhavandgarMargaret BeachEileen PelayoBrian WalittSarfaraz A Hasni Mariana J KaplanMayank TandonMaria Teresa MagoneDavid E KleinerJohn A ChioriniAlan BaerBlake M Warner

Published in: Annals of the rheumatic diseases (2024)

SjD patients' tissues exhibit increased expression of ISGs and activation of the JAK-STAT pathway in a cell type-dependent manner. JAKi normalises this aberrant signalling at the tissue level and in PBMCs, suggesting a putative viable therapy for SjD, targeting both glandular and extraglandular symptoms. Predicated on these data, a phase Ib/IIa randomised controlled trial to treat SjD with tofacitinib was initiated.

Keyphrases

end stage renal disease
newly diagnosed
ejection fraction
oxidative stress
poor prognosis
rheumatoid arthritis
chronic kidney disease
gene expression
study protocol
prognostic factors
randomized controlled trial
clinical trial
cancer therapy
disease activity
big data
systemic lupus erythematosus
sleep quality