title: Lyse or not to lyse: Clinical significance of red blood cell autoantibodies.
abstract: Autoimmune hemolytic anemia (AIHA) is a rare autoimmune disease characterized by a hemolytic anemia caused by autoantibodies against red blood cells (RBCs). These autoantibodies are routinely detected via the direct antiglobulin test (DAT). As expected, the DAT score correlates with the presence of clinical symptoms, but this correlation is far from perfect. Regularly, strongly positive DAT scores are encountered with no sign of hemolysis, while severe hemolysis can be seen even in patients with a negative DAT score. Apparently, the mere amount of antibody is not the sole predictor of disease. In this paper, we review the current literature on aspects of both the autoantibodies and the patients' clearance system that together determine the clinical significance of an anti-RBC autoantibody, ranging from antibody isotype to antibody Fc-glycosylation to alternative clearance mechanisms. From this, the ensemble of tests is inferred that in our view best assesses the main determinants for pathogenicity of autoantibodies.
authors.affiliation: Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Center, University of Amsterdam, Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands. Electronic address: e.meulenbroek@sanquin.nl.
authors.forename: Elisabeth M
authors.initials: EM
authors.lastname: Meulenbroek
authors.affiliation: Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Center, University of Amsterdam, Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands. Electronic address: d.wouters@sanquin.nl.
authors.forename: Diana
authors.initials: D
authors.lastname: Wouters
authors.affiliation: Department of Hematology, Academic Medical Center, University of Amsterdam, Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands. Electronic address: s.s.zeerleder@amc.uva.nl.
authors.forename: Sacha S
authors.initials: SS
authors.lastname: Zeerleder
mesh_terms: D000744:Anemia, Hemolytic, Autoimmune / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D000915:Antibody Affinity; D000918:Antibody Specificity; D001323:Autoantibodies / Q000032:analysis* / Q000096:biosynthesis / Q000737:chemistry; D003298:Coombs Test / Q000706:statistics & numerical data*; D004912:Erythrocytes / Q000276:immunology* / Q000473:pathology; D006461:Hemolysis / Q000276:immunology; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000032:analysis* / Q000737:chemistry; D010587:Phagocytosis; D011485:Protein Binding
chemical_list: D001323:Autoantibodies; D007132:Immunoglobulin Isotypes
keywords: Autoantibodies; Autoimmune hemolytic anemia; Clinical significance; Diagnostic assays; Direct antiglobulin test; Red blood cells