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Review
. 2024 Sep 17;30(1):152.
doi: 10.1186/s10020-024-00922-8.

Navigating therapeutic challenges in VEXAS syndrome: exploring IL-6 and JAK inhibitors at the forefront

Xiao Xiao Li  1 , Wen Hui Huang  1 , Xiao Bin Yang  2 , Qi Lin Yang  3 , Yu Zheng  4 , Yong Bao Huo  1 , Ting Ting Xie  5 , Cheng Hui Huang  1 , Shui Lian Yu  6
Affiliations
Review

Navigating therapeutic challenges in VEXAS syndrome: exploring IL-6 and JAK inhibitors at the forefront

Xiao Xiao Li et al. Mol Med. .

Abstract

VEXAS syndrome, an uncommon yet severe autoimmune disorder stemming from a mutation in the UBA1 gene, is the focus of this paper. The overview encompasses its discovery, epidemiological traits, genetic underpinnings, and clinical presentations. Delving into whether distinct genotypes yield varied clinical phenotypes in VEXAS patients, and the consequent adjustment of treatment strategies based on genotypic and clinical profiles necessitates thorough exploration within the clinical realm. Additionally, the current therapeutic landscape and future outlook are examined, with particular attention to the potential therapeutic roles of IL-6 inhibitors and JAK inhibitors, alongside an elucidation of prevailing limitations and avenues for further research. This study contributes essential theoretical groundwork and clinical insights for both diagnosing and managing VEXAS syndrome.

Keywords: IL-6 Inhibitors; JAK–STAT; Tocilizumab; Treatment; VEXAS syndrome.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Fig. 1
Fig. 1
The figure was created with BioRender.com. A Common clinical features of VEXAS syndrome include characteristic vacuoles within bone marrow myeloid and erythroid precursor cells. B In various autoimmune disorders, plasmacytoid dendritic cells (pDCs) release IFN-γ to stimulate macrophage activation. Subsequently, activated macrophages secrete cytokines such as IL-1, IL-6, and IL-8, fostering T cell activation. Activated T cells, in turn, produce IFN-γ, TNF-α, and other cytokines, enhancing macrophage activation. Both pDCs and macrophages can induce B cell activation by secreting B cell activating factor (BAFF). T cells also contribute to B cell activation through the production of IL-4 and IL-21. Upon activation, B cells produce IL-6 and IL-10, facilitating plasma cell differentiation and autoantibody generation. The red arrows in the figure indicate elevated factors associated with VEXAS syndrome. C Factors associated with VEXAS syndrome include IL-6 and IFN-γ, which exert their effects via the JAK-STAT pathway
See this image and copyright information in PMC

References

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