{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T19:13:08Z","timestamp":1790363588096,"version":"4.1.0"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,8]],"date-time":"2021-06-08T00:00:00Z","timestamp":1623110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>B-cells have received little attention in axial spondyloarthritis (axSpA) and for this reason their role in pathogenesis remains unclear. However, there are indications that B-cells may be involved in the disease process. Our objective was to obtain insights into the composition of the peripheral B-cell compartment of axSpA patients compared to healthy donors (HD) and patients with primary Sj\u00f6gren\u2019s syndrome (pSS), a typical B-cell-associated autoimmune disease. Special emphasis was given to CD27-negative B-cells expressing low levels of CD21 (CD21<jats:sup>low<\/jats:sup> B-cells), since this subset is implicated in autoimmune diseases with strong involvement of B-cells. Transitional B-cells (CD38<jats:sup>hi<\/jats:sup>) were excluded from the analysis of the CD27<jats:sup>-<\/jats:sup>CD21<jats:sup>low<\/jats:sup> B-cell compartment. This study included 45 axSpA patients, 20 pSS patients and 30 HDs. Intriguingly, compared to HDs the frequency of CD27<jats:sup>-<\/jats:sup>CD38<jats:sup>low<\/jats:sup>CD21<jats:sup>low<\/jats:sup> B-cells was significantly elevated in both axSpA and pSS patients (P&amp;lt;0.0001 for both comparisons). The frequency of CD27<jats:sup>-<\/jats:sup>CD38<jats:sup>low<\/jats:sup>CD21<jats:sup>low<\/jats:sup> B-cells expressing the activation-induced immune markers T-bet and CD11c was decreased in axSpA patients compared to HDs. A higher proportion of CD27<jats:sup>-<\/jats:sup>CD38<jats:sup>low<\/jats:sup>CD21<jats:sup>low<\/jats:sup> B-cells expressed the chemokine receptor CXCR3 in axSpA compared to HDs, suggestive for active involvement of these cells in an inflammatory process. The frequency of CD27<jats:sup>-<\/jats:sup>CD38<jats:sup>low<\/jats:sup>CD21<jats:sup>low<\/jats:sup> B-cells in axSpA patients correlated positively with age and erythrocyte sedimentation rate. Furthermore, axSpA patients with extra-skeletal manifestations (ESM) showed increased frequencies of CD27<jats:sup>-<\/jats:sup>CD38<jats:sup>low<\/jats:sup>CD21<jats:sup>low<\/jats:sup> B-cells compared to patients without ESM. In conclusion, our findings are suggestive of active B-cell involvement in the pathogenesis of axSpA, against prevailing dogma.<\/jats:p>","DOI":"10.3389\/fimmu.2021.686273","type":"journal-article","created":{"date-parts":[[2021,6,8]],"date-time":"2021-06-08T05:28:46Z","timestamp":1623130126000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":31,"title":["CD27-CD38lowCD21low B-Cells Are Increased in Axial Spondyloarthritis"],"prefix":"10.3389","volume":"12","author":[{"given":"Rick","family":"Wilbrink","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anneke","family":"Spoorenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Arends","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kornelis S. 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