Identification of candidate dysregulated lncRNAs and predicted lncRNA–miRNA interactions in antiphospholipid syndrome via cross−dataset transcriptomic analysis

Antiphospholipid syndrome (APS) is a systemic autoimmune thrombotic disorder characterised by persistent antiphospholipid antibodies (aPL) and recurrent thrombosis or pregnancy morbidity. Seronegative APS (SNAPS)—clinically indistinguishable from seropositive APS but persistently antibody-negative—represents a major unresolved diagnostic challenge. Non-coding RNAs (ncRNAs), particularly long non-coding RNAs (lncRNAs) acting through competing endogenous RNA (ceRNA) mechanisms, may constitute a missing mechanistic layer in APS pathogenesis. A cross-dataset comparative bioinformatic analysis was performed using three publicly available GEO datasets: GSE102215 (9 APS vs 9 HC, neutrophils, RNA-seq, discovery), GSE50395 (3 APS vs 3 HC, monocytes, microarray, exploratory replication), and GSE312344 (3 obstetric APS vs 3 HC, plasma exosomal RNA, lncRNA replication). DESeq2 and limma were used for differential expression; clusterProfiler for pathway enrichment; STRINGdb for PPI network; miRNet 2.0 for predicted lncRNA–miRNA interaction network. A pilot machine learning analysis is reported in supplementary material. DESeq2 identified 2,425 significant DEGs including a prominent IFN signature (IFIT1 log2FC=+3.13, MX1 log2FC=+2.32, STAT1 log2FC = + 1.12). GSEA revealed transcriptomic enrichment of NET formation (NES=1.87) and Proteasome (NES=2.15) pathways. PPI analysis identified STAT1 as the top hub gene (degree=160). Twenty-four candidate dysregulated lncRNAs were identified in APS neutrophils, including MIR155HG (log2FC = − 2.25), LINC00515 (log2FC = − 3.38), and SNHG7 (log2FC = − 1.22). Predicted lncRNA–miRNA interaction network analysis identified SNHG7 as the top hub lncRNA (degree=70, betweenness=19,264). Exploratory cross-dataset comparison showed 67% directional concordance in GSE50395; SNHG7 showed nominal dysregulation in GSE312344. This purely computational study identifies candidate dysregulated lncRNAs and predicted lncRNA–miRNA interactions in APS neutrophils, providing a hypothesis-generating framework for future experimental validation. No seronegative APS patients were studied; seronegative APS implications are speculative.