title: Investigations into the role of anti-HLA class II antibodies in TRALI.
abstract: 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.
  
  
  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 (kappa = 0.448) and good concordance for class II antibodies (kappa = 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Joint Program in Transfusion Medicine, Harvard Medical School, and the Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: Grace S
authors.initials: GS
authors.lastname: Kao
authors.forename: Isabelle G
authors.initials: IG
authors.lastname: Wood
authors.forename: David M
authors.initials: DM
authors.lastname: Dorfman
authors.forename: Edgar L
authors.initials: EL
authors.lastname: Milford
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Benjamin
mesh_terms: D002448:Cell Adhesion / Q000276:immunology; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D007518:Isoantibodies / Q000097:blood* / Q000276:immunology; D008168:Lung / Q000098:blood supply / Q000473:pathology; D008297:Male; D008833:Microcirculation / Q000276:immunology / Q000473:pathology; D017713:Platelet Transfusion / Q000009:adverse effects*; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000276:immunology* / Q000473:pathology*
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007518:Isoantibodies