IgA2<sup>+</sup> B cells and IgA2 anti-dsDNA antibodies are selectively targeted by belimumab after rituximab therapy in systemic lupus erythematosus.
prospective_cohort · Level II
Where this comes from
- Record sourced from PubMed, PMID 40706590.
- Also identified by DOI 10.1016/j.xcrm.2025.102247 and PMC identifier 12432362.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
No theragnostic biomarkers exist for systemic lupus erythematosus (SLE) to enable a precision medicine approach. Baseline serum IgA2 anti-double-stranded DNA (dsDNA) antibody levels are associated with response to combination belimumab after rituximab therapy in SLE (BEAT-lupus trial, ISRCTN 47873003). Analysis of the CALIBRATE trial (NCT02260934) confirms that baseline IgA2 anti-dsDNA antibody levels are specifically associated with response to belimumab after rituximab (odds ratio [OR] = 16.9, confidence interval [CI]: 2.8-101, compared to rituximab alone-CALIBRATE and BEAT-lupus combined data). IgA2 anti-dsDNA antibody levels decrease alongside IgA2 expression in plasmablasts only after this combination treatment. Increased serum B cell-activating factor (BAFF) levels are associated with rising IgA2 anti-dsDNA antibody levels after rituximab. IgA2 plasmablasts have increased BAFF receptor and interleukin (IL)-10 expression compared to IgA1 plasmablasts and have a distinct integrin profile implicating a gut mucosal origin. These findings validate IgA2 anti-dsDNA antibodies as a theragnostic biomarker of response and provide mechanistic insight into the selective targeting of IgA2<sup>+</sup> B cells by combination belimumab after rituximab in SLE.
Medical subject headings
- Antibodies, Antinuclear
- Antibodies, Monoclonal, Humanized
- B-Lymphocytes
- Immunoglobulin A
- Lupus Erythematosus, Systemic
- Rituximab