Single-cell sequencing of immune cells from anticitrullinated peptide antibody positive and negative rheumatoid arthritis

Xunyao Wu, Yi Liu, Shanzhao Jin, Min Wang, Yuhao Jiao, Bo Yang, Xin Lu, Xin Ji, Yunyun Fei, Huaxia Yang, Lidan Zhao, Hua Chen, Yaran Zhang, Hao Li, Peter E. Lipsky, George C. Tsokos (), Fan Bai () and Xuan Zhang ()
Additional contact information
Xunyao Wu: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Yi Liu: Peking University
Shanzhao Jin: Peking University
Min Wang: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Yuhao Jiao: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Bo Yang: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Xin Lu: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Xin Ji: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Yunyun Fei: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, The Ministry of Education Key Laboratory
Huaxia Yang: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, The Ministry of Education Key Laboratory
Lidan Zhao: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, The Ministry of Education Key Laboratory
Hua Chen: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, The Ministry of Education Key Laboratory
Yaran Zhang: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Hao Li: Beth Israel Deaconess Medical Center, Harvard Medical School
Peter E. Lipsky: RILITE Research Institute and AMPEL BioSolutions
George C. Tsokos: Beth Israel Deaconess Medical Center, Harvard Medical School
Fan Bai: Peking University
Xuan Zhang: Chinese Academy of Medical Sciences

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract The presence or absence of anti-citrullinated peptide antibodies (ACPA) and associated disparities in patients with rheumatoid arthritis (RA) implies disease heterogeneity with unknown diverse immunopathological mechanisms. Here we profile CD45+ hematopoietic cells from peripheral blood or synovial tissues from both ACPA+ and ACPA- RA patients by single-cell RNA sequencing and identify subsets of immune cells that contribute to the pathogenesis of RA subtypes. We find several synovial immune cell abnormalities, including up-regulation of CCL13, CCL18 and MMP3 in myeloid cell subsets of ACPA- RA compared with ACPA+ RA. Also evident is a lack of HLA-DRB5 expression and lower expression of cytotoxic and exhaustion related genes in the synovial tissues of patients with ACPA- RA. Furthermore, the HLA-DR15 haplotype (DRB1/DRB5) conveys an increased risk of developing active disease in ACPA+ RA in a large cohort of patients with treatment-naive RA. Immunohistochemical staining shows increased infiltration of CCL13 and CCL18-expressing immune cells in synovial tissues of ACPA- RA. Collectively, our data provide evidence of the differential involvement of cellular and molecular pathways involved in the pathogenesis of seropositive and seronegative RA subtypes and reveal the importance of precision therapy based on ACPA status.

Date: 2021
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DOI: 10.1038/s41467-021-25246-7

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