Genome-wide peripheral blood transcriptome analysis of Arab female lupus and lupus nephritis

• Fifteen splice variants were differentially expressed between lupus and HC.
• Ninety nine splice variants were differentially expressed between LN and HC.
• Pathway analysis revealed 11 significant pathways in lupus and 12 in LN.
• Deregulated expression of individual variants indicates its role in etiology.
• Our study highlights the significance of alternate splicing in lupus and LN.

Systemic lupus erythematosus (lupus) is a genetically heterogeneous autoimmune disorder with an obscure etiology. With 92–94% of human genes exhibiting alternative splicing, gaining insights to such events may lead to better diagnostics. Herein, we explored the genome-wide peripheral blood transcriptome of lupus and its severe form lupus-nephritis (LN) compared to healthy controls (HC). Age/gender/ethnically-matched Arab females were tested using high-density arrays and statistical analysis was carried out using appropriate software. Analysis revealed 15 splice variants that are differentially expressed between lupus/HC and 99 variants between LN/HC (p ≤ 0.05, SI> or ≤ 0.5, Benjamin Hochberg-False discovery rate correction). Comparison between LN/lupus revealed 7 variants that significantly differed in expression. Pathway analysis of differentially spliced-genes postulated 11 significant pathways in lupus and 12 in LN (p < 0.05). Analysis of peripheral blood transcriptome possibly revealed signature causative genes that are alternatively spliced, signifying their clinical relevance. Present study is the first to reveal the significance of alternative variants in lupus and LN.