MSU crystal deposition contributes to inflammation and immune responses in gout remission
Hongchen Gu,
Hanqing Yu,
Ling Qin,
Hanjie Yu,
Yaxiang Song,
Guangqi Chen,
Dake Zhao,
Shu Wang,
Wen Xue,
Ling Wang,
Zisheng Ai,
Bei Xu,
Ai Peng
Affiliations
Hongchen Gu
Center for Nephrology and Clinical Metabolomics, Division of Nephrology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
Hanqing Yu
Center for Nephrology and Clinical Metabolomics, Division of Nephrology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
Ling Qin
Center for Nephrology and Clinical Metabolomics, Division of Nephrology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
Hanjie Yu
Center for Nephrology and Clinical Metabolomics, Division of Nephrology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
Yaxiang Song
Center for Nephrology and Clinical Metabolomics, Division of Nephrology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
Guangqi Chen
Center for Nephrology and Clinical Metabolomics, Division of Nephrology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
Dake Zhao
Center for Nephrology and Clinical Metabolomics, Division of Nephrology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
Shu Wang
Center for Nephrology and Clinical Metabolomics, Division of Nephrology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
Wen Xue
Center for Nephrology and Clinical Metabolomics, Division of Nephrology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
Ling Wang
Center for Nephrology and Clinical Metabolomics, Division of Nephrology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
Zisheng Ai
Department of Medical Statistics, Tongji University School of Medicine, Shanghai 200092, China
Bei Xu
Center for Nephrology and Clinical Metabolomics, Division of Nephrology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China; Corresponding author
Ai Peng
Center for Nephrology and Clinical Metabolomics, Division of Nephrology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China; Corresponding author
Summary: As a prominent feature of gout, monosodium urate (MSU) crystal deposition induces gout flares, but its impact on immune inflammation in gout remission remains unclear. Using single-cell RNA sequencing (scRNA-seq), we characterize the transcription profiling of peripheral blood mononuclear cells (PBMCs) among intercritical remission gout, advanced remission gout, and normal controls. We find systemic inflammation in gout remission with MSU crystal deposition at the intercritical and advanced stages, evidenced by activated inflammatory pathways, strengthened inflammatory cell-cell interactions, and elevated arachidonic acid metabolic activity. We also find increased HLA-DQA1high classic monocytes and PTGS2high monocytes in advanced gout and overactivated CD8+ T cell subtypes in intercritical and advanced gout. Additionally, the osteoclast differentiation pathway is significantly enriched in monocytes, T cells, and B cells from advanced gout. Overall, we demonstrate systemic inflammation and distinctive immune responses in gout remission with MSU crystal deposition, allowing further exploration of the underlying mechanism and clinical significance in conversion from intercritical to advanced stage.
