STING ASSOCIATED VASCULOPATHY

 STING-associated vasculopathy with onset in infancy (SAVI) is a rare autoinflammatory disease caused by gain-of-function mutations in the TMEM173 gene, leading to constitutive activation of the STING pathway. This results in excessive type I interferon production, causing systemic inflammation, vasculopathy, and interstitial lung disease (ILD).

Recent Therapeutic Approaches:

Given the central role of type I interferons in SAVI, Janus kinase (JAK) inhibitors, which block interferon signaling, have been explored as potential treatments:

• Baricitinib (JAK1/2 Inhibitor): A case involving a 2-year-old patient with a heterozygous STING mutation (p.V155M) presented with severe ILD. Treatment with baricitinib, combined with steroids, led to improvement in respiratory symptoms over a 14-month follow-up. However, laboratory markers, particularly autoimmune indices, showed limited improvement, and lung imaging remained largely unchanged, suggesting that while baricitinib may alleviate some clinical symptoms, it might not fully control the underlying inflammation in SAVI. citeturn0search0

• Tofacitinib (JAK3 Inhibitor): In a study of a family with a novel V194L mutation in the TMEM173 gene, two affected members were treated with tofacitinib. Both patients experienced complete recovery within one month of treatment, indicating that tofacitinib may be an effective therapeutic option for certain SAVI mutations. citeturn0search1

Conclusion:

JAK inhibitors, particularly tofacitinib, have shown promise in treating SAVI, especially in cases with specific TMEM173 mutations. However, responses can vary, and some patients may experience partial improvement, as seen with baricitinib. These findings underscore the need for personalized treatment strategies and further research to optimize therapeutic approaches for SAVI.