Type I interferon as a pre-lupus marker in anti-nuclear antibody-associated childhood immune thrombocytopenic purpura

Abstract

Paediatric-onset anti-nuclear antibody-associated immune thrombocytopenic purpura (ITP-ANA+) is a pre-lupus condition. Interferon signature (IS) is a reliable method to measure interferon-stimulated gene expression which is commonly raised in systemic lupus erythematosus (SLE) and in adult pre-lupus cases. Between 2022 and 2024, IS analysis was performed on 61 children, 17 with ITP-ANA+, 15 with ITP-ANA-, 15 with SLE and 14 with juvenile idiopathic arthritis. IS was positive in 14/17 children (82%), with a median score of 17 (1.2-143). This median IS was significantly higher than in the ITP-ANA- group (2.8, 1-41, p = 0.03) and lower than in the SLE group (37.5, 2.1-129, p = 0.04). Among ITP-ANA+ children, IS elevation was associated with age >10 years at ITP diagnosis, newly diagnosed or persistent ITP, positive anti-extractable nuclear antigen antibodies and the absence of hydroxychloroquine treatment. Hydroxychloroquine significantly reduced IS values in three children with pre- and post-treatment scores available. The involvement of type I interferon signalling in childhood ITP-ANA+ highlights a distinct pathogenic pathway and IS appears as a pertinent biomarker to identify patients at risk of progression to SLE. The introduction of hydroxychloroquine in these patients could help prevent the high morbidity of SLE at adult age.

Keywords: anti‐nuclear antibody; children; immune thrombocytopenic purpura; incomplete lupus erythematosus; type 1 interferon.