Lupus & antiphospholipid syndrome
Gene Expression and Autoantibody Analysis Revealing Distinct Ancestry‐Specific Profiles Associated With Response to Rituximab in Refractory Systemic Lupus Erythematosus
Authors' conclusion
Ancestry appears central to the immunologic and clinical heterogeneity in SLE.
Study context
- Population
- Patients with active systemic lupus erythematosus (SLE) refractory to standard therapy, multiethnic UK cohort, British Isles Lupus Assessment Group (BILAG) Biologics Register110 assessed for rituximab response
- Participants
- 213 patients
- Exposure
- Gene expression clusters by ancestry and response to rituximab
- Outcome
- Response to first-cycle rituximab (BILAG 2004 disease activity)
- Follow-up
- 6 months from treatment start
Methodological detailsregistry-based (BILAG Biologics Register), multiethnic, hierarchical clustering
- Registry-based (BILAG Biologics Register)
- Multiethnic
- Hierarchical clustering
Main finding
As reported in the abstract
Response to rituximab by gene expression cluster · 6 months
- Non-European ancestry: 3 distinct clusters with stratified responses to rituximab, not explained by sociodemographic and clinical variables; lowest in interferon-low, neutrophil-high cluster, highest in cluster with high expression across all signatures
- P < 0.001
Observational data: associations, not effects.
Further findings
Interferon gene expression scores by ancestry · baseline
- Lower in European ancestry than in all other ancestry groups
- Relationship of interferon scores with plasmablast, neutrophil, myeloid lineage, inflammation and erythropoiesis scores differed between European and non-European ancestries
Autoantibodies
- In both ancestral groups, interferon-high clusters associated with U1 RNP/Sm antibodies
Original publication
Gene Expression and Autoantibody Analysis Revealing Distinct Ancestry‐Specific Profiles Associated With Response to Rituximab in Refractory Systemic Lupus Erythematosus. Arthritis Rheumatol. Published 22 March 2023. doi:10.
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