Abstract
Janus-kinase (JAK) and signal transduction activator of transcription (STAT) signal transduction pathway is involved in a wide range of physiological and pathological processes, including in the pathogenesis of several autoimmune diseases. Data supporting the role of JAK/STAT in the development of vasculitis are limited and mostly focused on large vessel vasculitis and Behçet’s disease. In this review, we provide a thorough picture of currently available evidence on the topic, gathered from in vitro experiments, animal models and human real-life data, analyzing the rationale for the use of JAK inhibitors for the management of vasculitis. Overall, despite a very strong biological and pathogenic basis, data are too few to recommend this therapeutic approach, beyond very severe and refractory forms of vasculitis. However, for the same reasons, a strong scientific effort in this direction is indeed worthwhile.
Highlights
Vasculitides are a heterogeneous group of systemic inflammatory diseases characterized by the inflammation of the wall of blood vessels
The pathogenesis of Behçet’s disease (BD) is profoundly different from that of giant cell arteritis (GCA) and Takayasu arteritis (TKA), showing a far greater involvement of the innate immune system
As an example of conflicting data, an Iranian study found that the gene of suppressor of cytokine signaling (SOCS) 1, a negative regulator of JAK/signal transduction activator of transcription (STAT) pathway, was hypermethylated in BD patients compared to healthy controls (HC)
Summary
Vasculitides are a heterogeneous group of systemic inflammatory diseases characterized by the inflammation of the wall of blood vessels. Numerous selective JAK inhibitors are currently under investigation, it is still not clear whether they will provide a real advantage for the management of inflammatory diseases (Schwartz et al, 2016) To our knowledge, this is the first published review presenting all currently available data on the potential benefit of the use of JAK inhibitors for the treatment of vasculitides. Despite their etiology remains elusive, there is strong evidence supporting one or more antigens as the triggering factors at the basis of a dysregulated immune response and a consequent selfsustaining chronic inflammation in the context of a genetic predisposition (Carmona et al, 2015; Carmona et al, 2017; Hatemi et al, 2018; Zhang et al, 2018; Régnier et al, 2020) Despite these forms of vasculitis share common features, such as vessel wall infiltration by immune cells, intimal hyperplasia, aneurysm formation, dissection and stenosis, the pathogenic process and cellular subsets involved are distinct. Due to its widespread biological functions, JAK/STAT pathway is potentially involved in all the pathogenic phenomena leading to the development of GCA, TKA and BD
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