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Here we profile CD45\n                    <jats:sup>+<\/jats:sup>\n                    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\n                    <jats:italic>CCL13<\/jats:italic>\n                    ,\n                    <jats:italic>CCL18<\/jats:italic>\n                    and\n                    <jats:italic>MMP3<\/jats:italic>\n                    in myeloid cell subsets of ACPA- RA compared with ACPA+ RA. Also evident is a lack of\n                    <jats:italic>HLA-DRB5<\/jats:italic>\n                    expression and lower expression of cytotoxic and exhaustion related genes in the synovial tissues of patients with ACPA- RA. Furthermore, the\n                    <jats:italic>HLA-DR15<\/jats:italic>\n                    haplotype (\n                    <jats:italic>DRB1<\/jats:italic>\n                    \/\n                    <jats:italic>DRB5<\/jats:italic>\n                    ) 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.\n                  <\/jats:p>","DOI":"10.1038\/s41467-021-25246-7","type":"journal-article","created":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T06:03:49Z","timestamp":1629180229000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":185,"title":["Single-cell sequencing of immune cells from anticitrullinated peptide antibody positive and negative rheumatoid arthritis"],"prefix":"10.1038","volume":"12","author":[{"given":"Xunyao","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2990-5738","authenticated-orcid":false,"given":"Yi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3939-4978","authenticated-orcid":false,"given":"Shanzhao","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhao","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunyun","family":"Fei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaxia","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaran","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9287-1676","authenticated-orcid":false,"given":"Peter E.","family":"Lipsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9589-2360","authenticated-orcid":false,"given":"George C.","family":"Tsokos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6119-8936","authenticated-orcid":false,"given":"Fan","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8775-1699","authenticated-orcid":false,"given":"Xuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,17]]},"reference":[{"key":"25246_CR1","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1038\/nrrheum.2011.28","volume":"7","author":"NA Daha","year":"2011","unstructured":"Daha, N. 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