Transcriptomic Analysis Suggests Overlapping Molecular Pathogenesis in JIA-Associated and ANA-Positive Uveitis

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.

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.

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.

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.