Investigations into the role of anti-HLA class II antibodies in TRALI

• Published in: Transfusion (Philadelphia, Pa.) Vol. 43; no. 2; pp. 185 - 191
• Main Authors: Kao, Grace S., Wood, Isabelle G., Dorfman, David M., Milford, Edgar L., Benjamin, Richard J.
• Format: Journal Article
• Language: English
• Published: Boston, MA, USA Blackwell Science Inc 01-02-2003; Blackwell Publishing
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis; Cell Adhesion - immunology; Endothelium, Vascular - immunology; Endothelium, Vascular - pathology; Female; Histocompatibility Antigens Class I - immunology; Histocompatibility Antigens Class II - immunology; Humans; Immunohistochemistry; Isoantibodies - blood; Isoantibodies - immunology; Lung - blood supply; Lung - pathology; Male; Medical sciences; Microcirculation - immunology; Microcirculation - pathology; Platelet Transfusion - adverse effects; Respiratory Distress Syndrome, Adult - etiology; Respiratory Distress Syndrome, Adult - immunology; Respiratory Distress Syndrome, Adult - pathology; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Human; HLA-System; Transfusion; Antibody; Pathogenesis; Class II histocompatibility antigen; Complication; Blood
• ISSN: 0041-1132; 1537-2995
• DOI: 10.1046/j.1537-2995.2003.00285.x

BACKGROUND : TRALI is thought to be triggered by recipient‐specific anti‐HLA class I or antibodies against neutrophils in donor plasma. Recently, anti‐HLA class II have also been implicated. The prevalence of anti‐HLA class II was investigated in normal volunteer platelet donors and in two nonfatal TRALI cases utilizing a flow‐based assay. Potential target antigens also were investigated.
STUDY DESIGN AND METHODS : Commercial flow cytometry‐based assays (FlowPRA, One Lambda, Inc.) for anti‐HLA class I and II were compared with standard lymphocytotoxicity tests. Subsequently, 151 volunteer platelet donors and two clinical cases of TRALI were screened with FlowPRA. Immunohistochemical studies were performed on lung tissue from a surgical case, an autopsy case, and a fatal TRALI case.
RESULTS : The FlowPRA assays showed moderate concordance for anti‐HLA class I (κ = 0.448) and good concordance for class II antibodies (κ = 0.801), when compared to standard lymphocytotoxicity assays. Ten and 9 percent of female platelet donors were positive for anti‐HLA class I and class II, respectively. Two nonfatal cases of TRALI showed both anti‐HLA class I and anti‐HLA class II. Immunohistochemical analysis of a TRALI case revealed granulocyte aggregation in alveolar capillaries with activated vascular endothelial cells. HLA class II antigen expression was not present on vascular endothelium or intravascular WBCs; however, strong expression was seen on alveolar macrophages.
CONCLUSION : FlowPRA assays often detect anti‐HLA class I not detected by conventional lymphocytotoxicity assays. These assays reveal anti‐HLA class II in normal female donor plasma and in sera implicated in TRALI. Immunohistochemical studies failed to reveal endothelial or intravascular‐WBC HLA class II antigen expression in lung tissue derived from TRALI cases or controls, but demonstrated HLA class II expression on pulmonary macrophages.