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Single-cell transcriptome analyses reveal disturbed decidual homoeostasis in obstetric antiphospholipid syndrome
  1. Chenyang Lu1,2,
  2. Rui Gao3,4,
  3. Pingying Qing1,
  4. Xun Zeng3,4,
  5. Xin Liao4,5,
  6. Meng Cheng4,6,
  7. Lang Qin3,4,
  8. Yi Liu1
  1. 1Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
  2. 2Division of Rheumatology, Department of Internal Medicine, The Third Affiliated Hospital of Sun Yet-Sen University, Guangzhou, Guangdong, China
  3. 3Reproductive Medical Center, Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China
  4. 4Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China
  5. 5Department of the Central Operating Unit, West China Second University Hospital, Sichuan University/West China School of Nursing, Chengdu, Sichuan, China
  6. 6Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China
  1. Correspondence to Dr Lang Qin, Reproductive Medical Center, Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, People's Republic of China; cacier{at}163.com; Professor Yi Liu, Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People's Republic of China; yiliu8999{at}wchscu.cn

Abstract

Objectives Obstetric antiphospholipid syndrome (OAPS) is an autoimmune disease characterised by the presence of antiphospholipid antibodies in circulation and pathological pregnancy. However, the pathogenesis of OAPS remains unknown. We aimed to reveal cellular compositions and molecular features of decidual cells involved in the development of OAPS using single-cell RNA sequencing (scRNA-seq).

Methods We performed unbiased scRNA-seq analysis on the first-trimester decidua from five OAPS patients and five healthy controls (HCs), followed by validations with flow cytometry, immunohistochemical staining and immunofluorescence in a larger cohort. Serum chemokines and cytokines were measured by using ELISA.

Results A higher ratio of macrophages but a lower ratio of decidual natural killer (dNK) cells was found in decidua from OAPS compared with HCs. Vascular endothelial cells shrinked in OAPS decidua while having upregulated chemokine expression and conspicuous responses to IFN-γ and TNF-α. Macrophages in OAPS had stronger phagocytosis function, complement activation signals and relied more on glycolysis. dNK cells were more activated in OAPS and had enhanced cytotoxicity and IFN-γ production. Downregulation of granules in OAPS dNK cells could be associated with suppressed glycolysis. Moreover, stromal cells had a prosenescent state with weakened immune surveillance for senescent cells in OAPS. In addition, the cellular interactions between decidual immune cells and those of immune cells with non-immune cells under disease state were altered, especially through chemokines, IFN-γ and TNF-α.

Conclusion This study provided a comprehensive decidual cell landscape and identified aberrant decidual microenvironment in OAPS, providing some potential therapeutic targets for this disease.

  • Antibodies, Antiphospholipid
  • Antiphospholipid Syndrome
  • Autoimmune Diseases
  • Inflammation
  • Autoimmunity

Data availability statement

Data are available in a public, open access repository. The reported data in this study are available in OMIX database, National Center for Bioinformation/Beijing Institute of Genomics, Chinese Academy of Sciences (https://ngdc.cncb.ac.cn/omix/) under the accession No. of OMIX004662.

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Data availability statement

Data are available in a public, open access repository. The reported data in this study are available in OMIX database, National Center for Bioinformation/Beijing Institute of Genomics, Chinese Academy of Sciences (https://ngdc.cncb.ac.cn/omix/) under the accession No. of OMIX004662.

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Footnotes

  • Handling editor Josef S Smolen

  • CL and RG contributed equally.

  • Contributors CL, RG, PQ and LQ designed the study. RG, XZ, XL and MC collected the samples. CL and RG performed the data analysis and wrote the manuscript. RG and CL performed validation experiments. YL and LQ revised the manuscript and supervised the whole project. All authors approved the final manuscript. CL is the guarantor of this study.

  • Funding This study was funded by National Natural Science Foundation of China (82104484, 82101717), the 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University (ZYJC18003), Sichuan Province Science and Technology Department (2022ZYD0067, MZGC20230024), and the Natural Science Foundation of Sichuan Province (2022NSFSC1542).

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.