Reduced Erythrocyte Opsonization by Calreticulin, Lactadherin, Mannose-binding Lectin, and Thrombospondin-1 in MAFLD Patients.

INTRODUCTION

Metabolism dysfunction associated with fatty liver disease During metabolic hepatic inflammation (MAFLD), is characterized by systemic metabolism deregulation leading to increased hepatic erythrophagocytosis and subsequent iron overload and ferroptosis. Studies in animal models have shown that erythrocyte phosphatidylserine exposure drives erythrophagocytosis. However, the mechanism of erythrophagocytosis in human MAFLD has not been fully elucidated yet. Therefore, in this study, we explored the opsonins recognizing phosphatidylserine. In particular, we measured the levels of erythrocyte calreticulin, lactadherin, mannose-binding lectin, and thrombospondin-1.

METHODS

Twenty-four patients (15 men and 9 women) with MAFLD and 9 healthy controls (4 men and 5 women) were enrolled. Erythrocytes were isolated from EDTA-containing blood through multiple centrifugations and isotonic buffer. Protein levels were measured in erythrocyte lysates (triton X-100 0.1% v/v) or plasma with enzyme-linked immunosorbent assays.

RESULTS

Erythrocyte TSP-1 levels were reduced in MAFLD patients. This reduction was not followed by changes in plasma TSP-1 levels or erythrocyte calreticulin, lactadherin, and mannose- binding protein.

DISCUSSION: Our results suggest that erythrophagocytosis in human MALFD, unlike animal models, is not mediated by opsonization of exposed phosphatidylserine.

CONCLUSION

Our study underlines the need for disease models that could better reflect the molecular pathogenesis of human MAFLD.