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B Cell Kinetics upon Therapy Commencement for Active Extrarenal Systemic Lupus Erythematosus in Relation to Development of Renal Flares: Results from Three Phase III Clinical Trials of Belimumab
Örebro University, School of Medical Sciences. Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, 17176 Stockholm, Sweden; Department of Rheumatology, Faculty of Medicine and Health, Örebro University, 70281 Örebro, Sweden.ORCID iD: 0000-0002-4875-5395
Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, 17176 Stockholm, Sweden.
Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, 17176 Stockholm, Sweden.
Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, 17176 Stockholm, Sweden.
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2022 (English)In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 23, no 22, article id 13941Article in journal (Refereed) Published
Abstract [en]

Renal flares constitute major determinants of poor prognosis in people living with systemic lupus erythematosus (SLE). The aim of the present study was to investigate changes in B cell subsets in relation to renal flares upon initiation of standard therapy (ST) plus belimumab or placebo in patients with SLE. Using data from the BLISS-76, BLISS-SC, and BLISS Northeast Asia trials, we investigated associations of relative to baseline rapid (through week 8) and early (through week 24) percentage changes in circulating CD19+ B cell subsets characterised through flow cytometry, anti-dsDNA antibodies, and complement levels with the occurrence of renal flares over one year. Patients who developed renal flares showed more prominent rapid decreases in CD19+CD20+CD138+ short-lived plasma cells (-50.4% vs. -16.7%; p = 0.019) and CD19+CD20-CD27bright plasmablasts (-50.0% vs. -29.9%; p = 0.020) compared to non-flaring patients, followed by a subsequent return. Less prominent rapid reductions in CD19+CD27-CD24brightCD38bright transitional B cells (-42.9% vs. -75.0%; p = 0.038) and CD19+CD20-CD138+ peripheral long-lived plasma cells (-11.3% vs. -29.2%; p = 0.019) were seen in belimumab-treated-but not placebo-treated-patients who developed renal flares compared to belimumab-treated patients who did not. Rapid and early changes in anti-dsDNA or complement levels showed no clear association with renal flares. In summary, a rapid drop followed by a subsequent return in circulating short-lived plasma cells and plasmablasts upon treatment for active extra-renal SLE portended renal flares, indicating a need for therapeutic adjustments in patients showing such B cell patterns. Rapid decreases in transitional B cells and peripheral long-lived plasma cells upon belimumab therapy commencement may signify a greater protection against renal flares. B cell kinetics may prove useful in early drug evaluation.

Place, publisher, year, edition, pages
MDPI, 2022. Vol. 23, no 22, article id 13941
Keywords [en]
B cells, B lymphocyte, belimumab, biologics, biomarkers, plasma cells, renal flares, systemic lupus erythematosus
National Category
Rheumatology and Autoimmunity
Identifiers
URN: urn:nbn:se:oru:diva-102442DOI: 10.3390/ijms232213941ISI: 000887479000001PubMedID: 36430417Scopus ID: 2-s2.0-85142849998OAI: oai:DiVA.org:oru-102442DiVA, id: diva2:1714066
Funder
Swedish Rheumatism Association, R-969696King Gustaf V Jubilee Fund, FAI-2020-0741 FAI-2020-0663Swedish Society of Medicine, SLS-974449Region Stockholm, FoUI-955483Karolinska InstituteNyckelfonden, OLL-974804
Note

Funding agency:

Professor Nanna Svartz Foundation 2020-00368

Ulla and Roland Gustafsson Foundation 2021-26

Available from: 2022-11-28 Created: 2022-11-28 Last updated: 2022-12-07Bibliographically approved

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Parodis, Ioannis

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