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 /
This study aimed to identify and validate novel autoantibodies that reflect global and organ-specific disease activity in systemic lupus erythematosus (SLE).Plasma samples were screened for IgG and IgA seroreactivity against 1609 protein autoantigens using a microarray (i-Ome Discovery; Sengenics)....
Elmentve itt :
| Szerzők: | |
|---|---|
| Dokumentumtípus: | Cikk |
| Megjelent: |
2025
|
| Sorozat: | ANNALS OF THE RHEUMATIC DISEASES
84 No. 7 |
| Tárgyszavak: | |
| doi: | 10.1016/j.ard.2025.04.008 |
| mtmt: | 36162434 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/36899 |
| Tartalmi kivonat: | This study aimed to identify and validate novel autoantibodies that reflect global and organ-specific disease activity in systemic lupus erythematosus (SLE).Plasma samples were screened for IgG and IgA seroreactivity against 1609 protein autoantigens using a microarray (i-Ome Discovery; Sengenics). We determined differentially abundant autoantibodies (daAAbs) in patients with SLE vs healthy controls within a discovery (n = 196 vs n = 110; NTC02890121) and an independent validation cohort (n = 30 vs n = 83; NCT02890134) from the European PRECISESADS project. Validated daAAbs were analysed in relation to global and organ-specific disease activity using linear and logistic regression, along with daAAb target pathway enrichment analysis.We validated 89 IgG and 66 IgA daAAbs. IgG anti-LIN28A, IgG anti-HMGN5, and both isotypes for anti-IRF5 and anti-TGIF1 were associated with a SLE disease activity index 2000 score of ≥10, negatively associated with lupus low disease activity state, and highly prevalent in subgroups with active disease across organ manifestations. IgG anti-LIN28A levels exceeded the cutoff for positivity in 53% of patients with central nervous system (CNS) involvement, a prevalence higher than that observed for anti-double-stranded DNA (20%) and 47% of patients with renal activity. A cluster of IgG and IgA daAAbs against RNA-binding proteins, including anti-LIN28A, was linked to CNS involvement. IgA anti-FOSL2 was elevated uniquely in patients with musculoskeletal activity. Enriched pathways involving DNA binding and repair showed considerable overlap across manifestations.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. |
|---|---|
| Terjedelem/Fizikai jellemzők: | 1164-1179 |
| ISSN: | 0003-4967 |