Soluble TNF-α receptor 2 produced by alternative splicing is paradoxically associated with markers of liver injury

Tumor necrosis factor-α and insulin resistance play central roles in the pathogenesis of abnormal hepatocellular function. We evaluate the relationship between a novel serum DS-TNFR2 (an alternatively spliced soluble TNF-α receptor 2) isoform and parameters of liver health. Serum ALT, AST and GGT, insulin resistance, adiponectin and DS-TNFR2 isoform concentrations were measured in 492 subjects from two different Caucasian Spanish populations. We found a significant negative association between serum ALT and DS-TNFR2 levels in both populations (r = − 0.269; p = 0.002 and r = − 0.152; p = 0.01, respectively). DS-TNFR2 levels also correlated negatively with serum AST (r = − 0.142; p = 0.042) and GGT (r = − 0.206; p = 0.003) in population 1 and with AST (r = − 0.127; p = 0.038) in population 2. In multiple regression analysis models, serum DS-TNFR2 was shown to be an independent modulator of serum ALT activity after adjusting for sex, age, BMI, HOMA and adiponectin in both populations. These results suggest potential anti-inflammatory properties of this TNF-α receptor 2 isoform at the hepatic level.