Serum mac-2 binding protein glycosylation isomer and matrix metalloproteinase-9 as predictive biomarkers for iron overload-induced liver fibrosis in sickle cell disease

Abstract

Background & Objective: Iron overload, a common complication of sickle cell disease (SCD), ultimately leads to liver fibrosis. Early detection is critical for successful management and noninvasive biomarkers can guide the clinicians. Mac-2 binding protein glycosylation isomer (M2BPGi) and matrix metalloproteinase (MMP-9) are potential biomarkers; however, their diagnostic utility in iron overload-induced liver fibrosis remains unclear. We evaluated the predictive efficacy of the serum M2BPGi and MMP-9 levels as biomarkers of iron overload-induced liver fibrosis in SCD patients.

Methodology: This case-control study involved 42 SCD patients and 50 healthy controls at the Genetic Hemoglobinopathies Center of Basra, Iraq. Three milliliters of whole blood were obtained via venipuncture from the patient and control groups and collected in gel separator vacuum blood collection tubes. Serum was separated and used for biochemical analyses. Serum M2BPGi and MMP-9 levels were determined via ELISA. Ferritin and liver function tests (LFT) were evaluated using automated analyzers.

Results: Significant increase in M2BPGi was recorded in SCD patients compared to the controls (37.39 ± 10.02 vs. 21.22 ± 6.36 pg/mL, P < 0.001). No significant difference in MMP-9 between SCD and control groups (406.45 ± 225.9 vs. 306.56 ± 270.85 ng/mL; (P = 0.068) respectively. The M2BPGi showed high sensitivity (93%) and high specificity (92%), with an area under curve (AUC) (94%), and was positively correlated with ferritin and LFT.

Conclusions: The M2BPGi is a promising non-invasive biomarker for detecting iron overload-induced liver fibrosis in SCD patients, whereas serum MMP-9 lacks the necessary sensitivity to be a reliable biomarker.

Abbreviations: AST: Serum aspartate, ALT: alanine aminotransferases, ECM: extracellular matrix, LFT: liver function tests, M2BPGi: Mac-2 binding protein glycosylation isomer, MMP-9: matrix metalloproteinase-9, SCD: sickle cell disease

Keywords: M2BPGi; Matrix Metalloproteinase-9; Sickle Cell Disease; Iron Overload; Liver Fibrosis

Citation: Thijeel KS, Thuwaini MM, Jasim AK, Abbas HJJ. Serum mac-2 binding protein glycosylation isomer and matrix metalloproteinase-9 as predictive biomarkers for iron overload-induced liver fibrosis in sickle cell disease. Anaesth. pain intensive care 2025;29(4):384-391. DOI: 10.35975/apic.v29i4.2826

Received: May 29, 2025; Revised: June 05, 2025; Accepted: June 06, 2025