Involvement of Human Leukocyte Antigen Class II Antibody in Pathogenesis of Transfusion-Related Acute Lung Injury (TRALI): Vascular Permeability Enhancement

Abstract

Vascular endothelial cells regulate the passage of fluids, solutes, and cells from the vascular space to the tis- sues. Disruption of vascular integrity is involved in the pathogenesis of inflammatory diseases including transfusion- related acute lung injury (TRALI), a most severe nonhemolytic transfusion reaction with symptoms such as dyspnea and/or hypotension and fever. Pulmonary edema, due to increased vascular permeability for macromolecules and plasma, is a hallmark of TRALI. The mortality rate of TRALI ranges from 5 to 10%. While donor antibodies (Abs) against human leukocyte antigen (HLA) class I and granulocytes are regarded as causative factors, various clinical studies have demon- strated the roles of anti-HLA class II-Ab on the etiology of TRALI, although the detailed mechanisms have not been clari- fied. Over several years we have investigated to clarify the underlying mechanism by which anti-HLA class II Abs cause an increase in endothelial permeability. In this review, we show that anti-HLA class II Ab generates proinflammatory cy- tokines and chemokines from HLA class II positive mononuclear cells of peripheral blood in an Fc R-dependent manner. As a result, the produced interleukin-1 and tumor necrosis factor- lead to increased endothelial permeability via the nu- clear factor- B pathway but not apoptosis of endothelial cells. These findings provide a better understanding of the roles of anti-HLA class II Ab in the etiology of TRALI.