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 BelimumabShow others and affiliations
2022 (English)In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 23, no 22, article id 13941
Article 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
2022-11-282022-11-282022-12-07Bibliographically approved