@article{10902/37496,
year = {2025},
url = {https://hdl.handle.net/10902/37496},
abstract = {Objectives: This study aimed to identify and validate novel autoantibodies that reflect global and organ-specific disease activity in systemic lupus erythematosus (SLE).
Methods: 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.
Results: 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.
Conclusions: 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.},
publisher = {BMJ Publishing Group},
publisher = {Annals of the Rheumatic Diseases, 2025, (7), 1164-1179},
title = {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},
author = {Lindblom, Julius and Lagutkin, Denis and Sherina, Natalia and Idborg, Helena and Beretta, Lorenzo and Borghi, Maria Orietta and Pers, Jacques Olivier and Saraux, Alain and Devauchelle Pensec, Valérie and Jousse Joulin, Sandrine and Lauwerys, Bernard and Ducreux, Julie and Maudoux, Anne Lise and Tavares, Ana and Almeida, Isabel and González-Gay Mantecón, Miguel Ángel and Alonso, Ricardo Blanco and Martínez, Alfonso Corrales and Rodríguez Pintó, Ignasi and Espinosa, Gerard},
}