5 Key Takeaways

• 1

  Patients with SLE had an increased ratio of long to short PRLR transcripts across multiple immune-cell populations compared with healthy donors.

• 2

  In patient PBMCs, splice-modulating oligomers targeting long PRLR reduced B-cell activation and shifted monocyte and natural killer cell populations toward more differentiated phenotypes.

• 3

  In 3 patient samples, treatment reduced expression of multiple IFN-stimulated genes, and experimental models showed reduced STAT1 phosphorylation and type I IFN signaling.

• 4

  After 8 weeks, treated lupus-prone mice had smaller glomerular tufts, fewer glomerular nuclei, and lower glomerular cellular density than control-treated mice.

• 5

  The study assessed early glomerular abnormalities, not established lupus nephritis or long-term renal outcomes, and its small ex vivo human samples do not establish clinical efficacy or safety.