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SSc displays disturbed lymphocyte homeostasis. Immunosuppressive medications targeting T or B cells can improve disease manifestations. SSc clinical manifestations and immunosuppressive medication in itself can cause changes in lymphocyte subsets. The aim of this study was to investigate peripheral lymphocyte homeostasis in SSc with regards to the immunosuppression and to major organ involvement. 44 SSc patients and 19 healthy donors (HD) were included. Immunophenotyping of peripheral whole blood by fluorescence-activated cell sorting was performed. Cytokine secretions of stimulated B cell cultures were measured. SSc patients without immunosuppression compared to HD displayed lower \u03b3\u03b4 T cells, lower T helper cells (CD3<jats:sup>+<\/jats:sup>\/CD4<jats:sup>+<\/jats:sup>), lower transitional B cells (CD19<jats:sup>+<\/jats:sup>\/CD38<jats:sup>++<\/jats:sup>\/CD10<jats:sup>+<\/jats:sup>\/IgD<jats:sup>+<\/jats:sup>), lower pre-switched memory B cells (CD19<jats:sup>+<\/jats:sup>\/CD27<jats:sup>+<\/jats:sup>\/IgD<jats:sup>+<\/jats:sup>), and lower post-switched memory B cells (CD19<jats:sup>+<\/jats:sup>\/CD27<jats:sup>+<\/jats:sup>\/IgD<jats:sup>\u2212<\/jats:sup>). There was no difference in the cytokine production of whole B cell cultures between SSc and HD. Within the SSc cohort, mycophenolate intake was associated with lower T helper cells and lower NK cells (CD56<jats:sup>+<\/jats:sup>\/CD3<jats:sup>\u2212<\/jats:sup>). The described differences in peripheral lymphocyte subsets between SSc and HD generate further insight in SSc pathogenesis. Lymphocyte changes under effective immunosuppression indicate how lymphocyte homeostasis in SSc might be restored.<\/jats:p>","DOI":"10.1007\/s00296-021-05034-8","type":"journal-article","created":{"date-parts":[[2021,10,25]],"date-time":"2021-10-25T08:03:41Z","timestamp":1635149021000},"page":"1373-1381","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Lymphocyte subsets in the peripheral blood are disturbed in systemic sclerosis patients and can be changed by immunosuppressive medication"],"prefix":"10.1007","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0074-4459","authenticated-orcid":false,"given":"Michael","family":"Gernert","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans-Peter","family":"Tony","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1935-2092","authenticated-orcid":false,"given":"Eva Christina","family":"Schwaneck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6320-4818","authenticated-orcid":false,"given":"Ottar","family":"Gadeholt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7745-3903","authenticated-orcid":false,"given":"Matthias","family":"Fr\u00f6hlich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3968-2849","authenticated-orcid":false,"given":"Jan","family":"Portegys","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3168-7074","authenticated-orcid":false,"given":"Patrick-Pascal","family":"Strunz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3289-2299","authenticated-orcid":false,"given":"Marc","family":"Schmalzing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,10,25]]},"reference":[{"key":"5034_CR1","doi-asserted-by":"publisher","first-page":"1685","DOI":"10.1016\/S0140-6736(17)30933-9","volume":"390","author":"CP Denton","year":"2017","unstructured":"Denton CP, Khanna D (2017) Systemic sclerosis. 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