Biomolecules · 2026
Transcriptomic Analysis Suggests Overlapping Molecular Pathogenesis in JIA-Associated and ANA-Positive Uveitis.
СтатьяНазвание и аннотация: Перевод в очереди
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Kasper Maren, Leyers Michelle, Witten Anika, Wortmann Charlotte, Walet Regina, Bauer Dirk, Schell Melanie, Petratou Kleio, Heinz Carsten, Lapp Thabo, Stoll Monika, Heiligenhaus Arnd
Аннотация
PURPOSE: Clinical presentation of anterior uveitis affecting the iris is nearly identical in patients with juvenile idiopathic-associated uveitis (JIAU) and patients with antinuclear antibody-positive anterior uveitis (ANA-U). This study investigates whether the iris transcriptomes of patients with JIAU or ANA-U differ or reflect the clinical homogeneity.
METHODS: Iris biopsies were obtained from patients with JIAU (n = 31) or ANA-U (n = 9) during trabeculectomy, iridectomy, or complex cataract surgery. Frozen iris tissues were homogenized, the RNA was isolated and analyzed using a bulk RNA sequencing approach. Genes with a Benjamini-Hochberg false discovery rate (FDR) p ≤ 0.05 and a log2 fold change (FC) of >1 or <-1 were defined as significantly differentially expressed genes (DEGs). Pathway enrichment analysis was subsequently performed to characterize these DEGs.
RESULTS: The JIAU group included nine male and 22 female patients (median age 10.2 [IQR 7.2, 13.7] years), while the ANA-U group consisted of one male and eight female patients (median age 10.2 years (IQR [6.1, 11.7]) years). No DEGs were identified when comparing the iris transcriptomes of JIAU and ANA-U directly. Subgroup analyses based on disease activity revealed 35 DEGs in ANA-U, one DEG in JIAU. Inter-group comparisons based on uveitis activity status yielded no DEGs. In the merged JIAU/ANA-U cohort, 28 DEGs were upregulated in the active vs. inactive uveitis. Regarding secondary glaucoma, 12 DEGs were identified in JIAU, and 15 DEGs were identified in the corresponding ANA-U subgroup. Inter-group comparisons based on glaucoma status yielded no DEGs. In the merged JIAU/ANA-U cohort, 20 DEGs were identified between patients with and without glaucoma.
CONCLUSIONS: Our findings reveal only marginal differences in gene expression patterns in iris tissues from JIAU and ANA-U patients. These results suggest a high degree of similarity in the underlying inflammatory processes of both uveitis subsets.
METHODS: Iris biopsies were obtained from patients with JIAU (n = 31) or ANA-U (n = 9) during trabeculectomy, iridectomy, or complex cataract surgery. Frozen iris tissues were homogenized, the RNA was isolated and analyzed using a bulk RNA sequencing approach. Genes with a Benjamini-Hochberg false discovery rate (FDR) p ≤ 0.05 and a log2 fold change (FC) of >1 or <-1 were defined as significantly differentially expressed genes (DEGs). Pathway enrichment analysis was subsequently performed to characterize these DEGs.
RESULTS: The JIAU group included nine male and 22 female patients (median age 10.2 [IQR 7.2, 13.7] years), while the ANA-U group consisted of one male and eight female patients (median age 10.2 years (IQR [6.1, 11.7]) years). No DEGs were identified when comparing the iris transcriptomes of JIAU and ANA-U directly. Subgroup analyses based on disease activity revealed 35 DEGs in ANA-U, one DEG in JIAU. Inter-group comparisons based on uveitis activity status yielded no DEGs. In the merged JIAU/ANA-U cohort, 28 DEGs were upregulated in the active vs. inactive uveitis. Regarding secondary glaucoma, 12 DEGs were identified in JIAU, and 15 DEGs were identified in the corresponding ANA-U subgroup. Inter-group comparisons based on glaucoma status yielded no DEGs. In the merged JIAU/ANA-U cohort, 20 DEGs were identified between patients with and without glaucoma.
CONCLUSIONS: Our findings reveal only marginal differences in gene expression patterns in iris tissues from JIAU and ANA-U patients. These results suggest a high degree of similarity in the underlying inflammatory processes of both uveitis subsets.