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VEXAS and Related Syndromes Share Immune Signatures

March 13, 2025
in Health News
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TOPLINE:

Shared inflammatory signatures in vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome, myelodysplasia cutis (MDS-cutis), and Sweet syndrome (SS) suggest interferon pathways as therapeutic targets.

METHODOLOGY:

  • Multicenter translational study in France compared 20 patients with cutaneous lesions (median age 67 years; 50% men) with five healthy control skin samples.
  • Lesion types were VEXAS syndrome, MDS-cutis, idiopathic SS, and leukemia cutis.
  • Bulk RNA sequencing and pathway enrichment analyses were conducted to identify differentially expressed genes and activated inflammatory pathways.

TAKEAWAY:

  • VEXAS, MDS-cutis, and SS lesions displayed closely related transcriptomic profiles characterized by cytokine-driven inflammation, interferon signatures, and apoptosis pathway activation.
  • VEXAS, MDS-cutis, and SS had a type 1 immune response with type 1 and 2 interferons, tumor necrosis factor (TNF), and interleukin-1 beta; leukemia cutis had a cell cycle–driven transcriptomic profile.
  • VEXAS syndrome showed specific downregulation of cytotoxic-related genes (GNLY, PRF1, GZMB) and the immune-checkpoint gene LAG3 compared with MDS-cutis.
  • Janus kinase inhibitors, particularly ruxolitinib, showed partial or complete responses in four patients.

IN PRACTICE:

“The findings of this translational study highlight a common inflammatory pattern shared between VEXAS syndrome, MDS-cutis, and refractory idiopathic SS skin samples,” the authors wrote. They said this suggests “the potential therapeutic targeting of interferon pathways in patients affected with refractory nonblastic myeloid-related skin diseases.”

SOURCE:

The study was led by Chloé Grolleau, MD, PhD, Department of Dermatology, Saint-Louis Hospital in Paris, France. It was published online on March 12 in JAMA Dermatology.

LIMITATIONS:

The study’s small sample size and heterogeneous inflammatory scores among patients limit its generalizability.

DISCLOSURES:

The study funding source was not reported. Grolleau reported receiving nonfinancial support from Sanofi outside the submitted work. Two authors disclosed receiving personal fees, grants, and nonfinancial support from pharmaceutical companies during this work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.



Source link : https://www.medscape.com/viewarticle/vexas-and-related-syndromes-share-immune-signatures-2025a1000632?src=rss

Author :

Publish date : 2025-03-13 07:34:00

Copyright for syndicated content belongs to the linked Source.

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