{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T04:00:18Z","timestamp":1793678418361,"version":"4.5.1"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2013,2,1]],"date-time":"2013-02-01T00:00:00Z","timestamp":1359676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Recent observations of abnormal immunoglobulin responses and case reports describing successful B-cell ablative therapy suggest involvement of B cells in the pathogenesis of sarcoidosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To investigate how abnormal B-cell maturation and function in patients with sarcoidosis contribute to disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with sarcoidosis (n = 32) were included for detailed analysis by immunohistochemistry of tissue, flow cytometry of blood B-cell subsets, and serum immunoglobulin levels. Vaccination responses in patients with sarcoidosis to influenza virus and encapsulated bacteria and molecular analysis of immunoglobulin heavy chain transcripts were studied for functional analysis of immunoglobulin responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Perigranuloma localization of IgA-producing plasma cells and numerous B cells were found in affected tissues. Total blood B-cell numbers were normal, CD27+ memory B cells were significantly reduced, and CD27\u2212IgA+ B cells were significantly increased; the results are normalized in patients treated with TNF-\u03b1 blockers. Despite this, patients had normal serum immunoglobulin levels and normal antigen-specific immunoglobulin responses. IgA and IgG transcripts, however, showed high frequencies of somatic hypermutations and increased usage of downstream IgG subclasses, suggestive for prolonged or repetitive responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The large B-cell infiltrates in granulomatous tissue and increased molecular signs of antibody maturation are indicative of direct involvement of B cells in local inflammatory processes in patients with sarcoidosis. Moreover, CD27\u2212IgA+ B cells could be a marker for treatment with TNF-\u03b1 blockers. These findings of B cells as emerging key players provide a rationale for a systematic study on B-cell ablative therapy in patients with sarcoidosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201206-1024oc","type":"journal-article","created":{"date-parts":[[2012,12,14]],"date-time":"2012-12-14T02:36:02Z","timestamp":1355452562000},"page":"406-416","source":"Crossref","is-referenced-by-count":82,"title":["Perigranuloma Localization and Abnormal Maturation of B Cells"],"prefix":"10.1093","volume":"187","author":[{"given":"Lieke S.","family":"Kamphuis","sequence":"first","affiliation":[{"name":"Department of Immunology"},{"name":"Section of Clinical Immunology, Department of Internal Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menno C.","family":"van Zelm","sequence":"additional","affiliation":[{"name":"Department of Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"King H.","family":"Lam","sequence":"additional","affiliation":[{"name":"Department of Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guus F.","family":"Rimmelzwaan","sequence":"additional","affiliation":[{"name":"Department of Virology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. 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