Institute Affiliations

Honors & Awards

  • Dean's Postdoctoral Fellowship, Stanford School of Medicine (2024-2025)
  • International Ph.D. fellowship, University of Lille, Doctoral School of Health and Biology (2018-2022)

Stanford Advisors

Contact

  • Academic
    smanasi@stanford.edu
    University - Scholar Department: Bioengineering Position: Postdoctoral Scholar

Additional Info

  • Mail Code: 4245

All Publications

  • Autoantibody hotspots reveal origin and impact of immunogenic XIST ribonucleoprotein complex. bioRxiv : the preprint server for biology Yan, B., Lee, J., Srinivasan, S., Shi, Q., Dou, D. R., Davuluri, S., Nandyala, S., Woods, A., Leatherman, G., Zhao, Y., Reggiardo, R. E., Sawant, M., Thiam, H. R., Shah, A. A., Fiorentino, D. F., Chung, L. S., Chang, H. Y. 2025

    Abstract

    Four out of five patients with autoimmune diseases are women. The XIST ribonucleoprotein (RNP) complex, comprising the female-specific long noncoding RNA XIST and over 100 associated proteins, may drive several autoimmune diseases that disproportionately affect women, who have elevated levels of autoantibodies against the XIST RNP. However, the structural distribution, potential origin, and clinical significance of XIST RNP autoantibodies remained unexplored. Here, we find that XIST RNP is associated with autoantigens associated with six female-biased autoimmune conditions. Mapping autoantibody targets to their occupancy sites on XIST shows that these autoantigens are concentrated at discrete "hotspots" along the XIST lncRNA, notably the A-repeat. Cell type-specific protein expression data nominated neutrophils as a predominant source of hotspot antigens, and we confirmed the presence of both XIST and hotspot antigens in neutrophil extracellular traps during NETosis, an immunogenic programmed cell death pathway triggered by neutrophil activation upon which neutrophils extrude their nuclear content. Furthermore, we found that levels of autoantibodies against a top hotspot antigen, SPEN, that binds the A-repeat, correlate with severe digital ischemia in systemic sclerosis in two independent cohorts. Together, these data show a plausible mechanism for the origin of AXA, guided by RNA structure and RNA-protein interactions, and show that antibodies to XIST RNP holds promise for disease endotyping and prognostication in female-biased autoimmune conditions.Novel autoantibodies target hotspots on XIST ribonucleoprotein complex in female-biased autoimmune diseases.

    View details for DOI 10.1101/2025.01.16.633465

    View details for PubMedID 39896599

    View details for PubMedCentralID PMC11785099