Lupus & antiphospholipid syndrome
Novel IgG and IgA autoantibodies validated in two independent cohorts are associated with disease activity and determine organ manifestations in systemic lupus erythematosus: implications for anti-LIN28A, anti-HMGN5, anti-IRF5, and anti-TGIF1
Authors' conclusion
Novel IgG and IgA autoantibodies, including IgG anti-LIN28A, IgG anti-HMGN5, IgG and IgA anti-IRF5, and IgG and IgA anti-TGIF1 were associated with SLE disease activity and highly abundant across organ manifestations.
Study context
- Population
- Patients with systemic lupus erythematosus (SLE) and healthy controls from the European PRECISESADS projectdiscovery and validation cohorts
- Participants
- 196 / 110 / 30 / 83
- Exposure
- Patients with SLE vs healthy controls
- SLE (discovery)n = 196
- Healthy controls (discovery)n = 110reference
- SLE (validation)n = 30
- Healthy controls (validation)n = 83reference
- Outcome
- Differentially abundant IgG and IgA autoantibodies (daAAbs) in SLE vs healthy controls, and their association with global and organ-specific disease activity
Methodological detailsautoantigen microarray screening (1609 protein autoantigens), discovery and independent validation cohorts, linear and logistic regression, pathway enrichment analysis
- Autoantigen microarray screening (1609 protein autoantigens)
- Discovery and independent validation cohorts
- Linear and logistic regression
- Pathway enrichment analysis
Main finding
As reported in the abstract
Validated daAAbs
Validated IgG differentially abundant autoantibodies (daAAbs)
89
Validated IgA daAAbs
66
Observational data: associations, not effects.
Further findings
IgG anti-LIN28A positivity by organ involvement
- IgG anti-LIN28A positive, patients with central nervous system (CNS) involvement
- 53%
- Anti-dsDNA positive, patients with CNS involvement
- 20%
- IgG anti-LIN28A positive, patients with renal activity
- 47%
Organ-specific autoantibody patterns
- Cluster of IgG and IgA daAAbs against RNA-binding proteins, including anti-LIN28A, linked to CNS involvement
- IgA anti-FOSL2 elevated uniquely in patients with musculoskeletal activity
- Enriched pathways involving DNA binding and repair showed considerable overlap across manifestations
Original publication
Novel IgG and IgA autoantibodies validated in two independent cohorts are associated with disease activity and determine organ manifestations in systemic lupus erythematosus: implications for anti-LIN28A, anti-HMGN5, anti-IRF5, and anti-TGIF1. Ann Rheum Dis. Published 9 May 2025. doi:10.
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