Dysregulation of Immune Cell Subpopulations in Atypical Hemolytic Uremic Syndrome

I. Ru Chen, Chiu Ching Huang, Siang Jyun Tu, Guei Jane Wang, Ping Chin Lai, Ya Ting Lee, Ju Chen Yen, Ya Sian Chang, Jan Gowth Chang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

1 Scopus citations


Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening thrombotic microangiopathy. Definitive biomarkers for disease diagnosis and activity remain elusive, making the exploration of molecular markers paramount. We conducted single-cell sequencing on peripheral blood mononuclear cells from 13 aHUS patients, 3 unaffected family members of aHUS patients, and 4 healthy controls. We identified 32 distinct subpopulations encompassing 5 B-cell types, 16 T- and natural killer (NK) cell types, 7 monocyte types, and 4 other cell types. Notably, we observed a significant increase in intermediate monocytes in unstable aHUS patients. Subclustering analysis revealed seven elevated expression genes, including NEAT1, MT-ATP6, MT-CYB, VIM, ACTG1, RPL13, and KLRB1, in unstable aHUS patients, and four heightened expression genes, including RPS27, RPS4X, RPL23, and GZMH genes, in stable aHUS patients. Additionally, an increase in the expression of mitochondria-related genes suggested a potential influence of cell metabolism on the clinical progression of the disease. Pseudotime trajectory analysis revealed a unique immune cell differentiation pattern, while cell—cell interaction profiling highlighted distinctive signaling pathways among patients, family members, and controls. This single-cell sequencing study is the first to confirm immune cell dysregulation in aHUS pathogenesis, offering valuable insights into molecular mechanisms and potential new diagnostic and disease activity markers.

Original languageEnglish
Article number10007
JournalInternational Journal of Molecular Sciences
Issue number12
StatePublished - 11 06 2023
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2023 by the authors.


  • atypical hemolytic uremic syndrome
  • complement
  • disease activity
  • single cell sequencing
  • therapy
  • Ribosomal Proteins/genetics
  • Leukocytes, Mononuclear/pathology
  • Humans
  • Neoplasm Proteins/genetics
  • Genes, Mitochondrial
  • Atypical Hemolytic Uremic Syndrome/genetics


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