Elevated Serum Levels of Cell Death Circulating Biomarkers, M30 and M65, In Patients with β-Thalassemia Major

Abstract

Deposition of iron in visceral organs, mainly in the liver, causes tissue damage in β-thalassemia major (β-TM) patients. Keratin 18 (K18) represents one of the major caspase substrates during apoptosis of hepatocytes. To better characterize the hepatic apoptosis and/or necrosis in β-thal patients, the circulating levels of M65 (soluble intact K18) and M30 (the caspases-generated K18 fragment) were measured in 40 β-TM patients and compared with 40 healthy controls. The ratio of M30/M65 (caspase-cleaved to total K18) was also determined in thalassemic and normal subjects. Results of the ELISA assays revealed that the serum levels of hepatocyte death markers, M65 and M30, were significantly increased in β-thal patients compared to healthy controls (p <0.0001). M30 serum levels were also positively correlated with the serum levels of liver transaminases including aspartate aminotransferase (AST) (r = 0.337, p = 0.047) and alanine aminotransferase (ALT) (r =0.391, p = 0.02).

• Apoptosis
• Keratin 18 (K18)
• Necrosis
• Aminotransferase