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Three features that related to the cells per unit of tissue were significantly increased in patients with both seronegative and seropositive RA compared with those with OA; on the other hand, aggregate features (number and diameter) were significantly increased in seropositive, but not seronegative, RA compared with OA. Aggregate diameter was associated with the gene expression of immunoglobulin heavy\u2010chain genes in the synovial tissue. Compared with blood, synovial immunoglobulin isotypes were skewed from <jats:italic>IGHM<\/jats:italic> and <jats:italic>IGHD<\/jats:italic> to <jats:italic>IGHG3<\/jats:italic> and <jats:italic>IGHG1<\/jats:italic>. Further, patients with RA with high levels of lymphocytic infiltrates in the synovium demonstrated parallel skewing in their blood with a relative decrease in <jats:italic>IGHGM<\/jats:italic> (<jats:italic>P<\/jats:italic> &lt;\u20090.002) and <jats:italic>IGHD<\/jats:italic> (<jats:italic>P<\/jats:italic> &lt;\u20090.03) and an increase in class\u2010switched immunoglobulin genes <jats:italic>IGHG3<\/jats:italic> (<jats:italic>P<\/jats:italic> &lt;\u20090.03) and <jats:italic>IGHG1<\/jats:italic> (<jats:italic>P<\/jats:italic> &lt;\u20090.002).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>High\u2010resolution automated identification and quantification of synovial immune cell aggregates uncovered skewing in the synovium from na\u00efve <jats:italic>IGHD<\/jats:italic> and <jats:italic>IGHM<\/jats:italic> to memory <jats:italic>IGHG3<\/jats:italic> and <jats:italic>IGHG1<\/jats:italic> and revealed that this process is reflected in the blood of patients with high inflammatory synovium.<\/jats:p><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/art42653-toc-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42653","type":"journal-article","created":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T13:25:57Z","timestamp":1689686757000},"page":"2137-2147","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Computer Vision Analysis of Rheumatoid Arthritis Synovium Reveals Lymphocytic Inflammation Is Associated With Immunoglobulin Skewing in Blood"],"prefix":"10.1002","volume":"75","author":[{"given":"Damon","family":"Frezza","sequence":"first","affiliation":[{"name":"The MITRE Corporation  McLean 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