MedComm (Nov 2024)

Comprehensive single‐cell profiling of monocytes in HLA‐B27‐positive ankylosing spondylitis with acute anterior uveitis

  • Huan Li,
  • Xueming Ju,
  • Lixin Zhang,
  • Jing Zhu,
  • Jing Zhang,
  • Jialing Xiao,
  • Ting Wang,
  • Weijia Wu,
  • Liang Wang,
  • Chengzi Gan,
  • Xiangmei Li,
  • Yutong Wei,
  • Siyu Zhu,
  • Yu Zhou,
  • Bolin Deng,
  • Ning Xiao,
  • Bo Gong

DOI
https://doi.org/10.1002/mco2.759
Journal volume & issue
Vol. 5, no. 11
pp. n/a – n/a

Abstract

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Abstract Acute anterior uveitis (AAU) is a common extra‐articular manifestation of ankylosing spondylitis (AS), particularly in patients positive for the human leucocyte antigen (HLA)‐B27 genetic marker. To explore the underlying mechanisms of HLA‐B27+ AS‐associated AAU, we employed single‐cell RNA sequencing to profile the transcriptomes of peripheral blood mononuclear cells in three HLA‐B27+ AS‐associated AAU patients and three healthy controls (HCs). We identified 11 distinct immune cell clusters, with a particular focus on monocytes, revealing six subsets, including three previously unidentified subsets, namely, GTPase immune‐associated proteins, Th17‐related, and lncRNA monocytes, with unique gene expression patterns. Significant differences in monocyte composition, activation states, and gene expression were observed between patients and HCs, particularly within HLA monocyte subpopulations. Notably, enhanced expression of X‐inactive specific transcript and myeloid cell nuclear differentiation antigen genes was validated across monocyte subclusters in patients. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis highlighted significant enrichment in antigen processing and presentation pathways, shedding light on the disease's molecular mechanisms. These findings provide novel insights into the molecular mechanisms of HLA‐B27+ AS‐associated AAU and may contribute to the development of targeted diagnostic and therapeutic strategies. Further clinical validation is essential.

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