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Antibody and cytokine profiles were measured in matched serum and synovial fluid (<jats:styled-content style=\"fixed-case\">SF<\/jats:styled-content>) samples from patients with Lyme arthritis. Synovial tissue from patients with antibiotic\u2010refractory arthritis was examined for histologic features, IgG subclasses of plasma cells, and messenger <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>) subclass expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>B burgdorferi<\/jats:italic> antibodies were primarily of the IgG1 and IgG3 subclasses, and the levels increased as the infection progressed. In contrast, <jats:styled-content style=\"fixed-case\">LD<\/jats:styled-content>\u2010associated autoantibodies were mainly of the IgG2 and IgG4 subclasses, and these responses were found primarily in patients with either antibiotic\u2010refractory or antibiotic\u2010responsive arthritis, particularly in <jats:styled-content style=\"fixed-case\">SF<\/jats:styled-content>. However, compared with the responsive group, the inflammatory milieu in <jats:styled-content style=\"fixed-case\">SF<\/jats:styled-content> in the refractory group was enriched for cytokines representative of innate, Th1, Th2, and Th17 responses. Synovial tissue in a subgroup of patients with refractory arthritis showed marked expression of <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> for IgG4 antibodies and large numbers of IgG4\u2010staining plasma cells. IgG4 autoantibodies in <jats:styled-content style=\"fixed-case\">SF<\/jats:styled-content> to each of the 3 <jats:styled-content style=\"fixed-case\">LD<\/jats:styled-content>\u2010associated autoantigens correlated with the magnitude of obliterative microvascular lesions and fibrosis in the tissue.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings indicate that the subclasses of IgG antibodies to <jats:italic>B burgdorferi<\/jats:italic> differ from those of <jats:styled-content style=\"fixed-case\">LD<\/jats:styled-content>\u2010associated autoantibodies. Furthermore, the correlation of IgG4 autoantibodies with specific synovial pathology in the refractory group suggests a role for these autoantibodies, either protective or pathologic, in antibiotic\u2010refractory Lyme arthritis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40566","type":"journal-article","created":{"date-parts":[[2018,5,23]],"date-time":"2018-05-23T03:25:00Z","timestamp":1527045900000},"page":"1835-1846","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Correlation of Lyme Disease\u2013Associated IgG4 Autoantibodies With Synovial Pathology in Antibiotic\u2010Refractory Lyme Arthritis"],"prefix":"10.1002","volume":"70","author":[{"given":"Katherine B.","family":"Sulka","sequence":"first","affiliation":[{"name":"Massachusetts General Hospital Harvard Medical School 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