title: Restriction in the repertoire of the immunoglobulin light chain subgroup in pathological cold agglutinins with anti-Pr specificity.
abstract: OBJECTIVE
  In cold agglutinin disease, monoclonal red blood cell autoantibodies, termed cold agglutinins, induce haemolysis in patients exposed to the cold. Commonly, these autoantibodies are directed against the developmentally regulated I/i blood groups. A second blood group system, the Pr system (located on glycophorins), is involved less frequently. Anti-Pr cold agglutinins recognize either alpha 2,3- or alpha 2,6-linked N-acetylneuraminic acid as the immunodominant group. Cold agglutinins of anti-I/i specificity show a remarkable restriction in their genomic repertoire of the immunoglobulin heavy and light-chain immunoglobulin-variable domain (i.e. exclusive use of VH4-34 in heavy chains). For anti-Pr cold agglutinins, preliminary data on the repertoire of the light-chain variable domain indicate a preference for the subgroup Vkappa IV. To elucidate restrictions in the light-chain variable-domain subgroup repertoire of anti-Pr cold agglutinins systematically, and to discuss these results in the context of their anti-Pr(1-3) subclassification and immunodominant sialic acid, light chains in 13 anti-Pr cold agglutinins were investigated.
  
  
  METHODS
  The anti-Pr light chains were isolated using temperature-dependent absorption/elution techniques. Subsequently, they were subjected to N-terminal Edman degradation, and the light chain Vkappa subgroup was affiliated using the Kabat database.
  
  
  RESULTS
  Five of 13 (38%) light chains belonged to Vkappa IV, five of 13 (38%) to Vkappa I and three of 13 (23%) to Vkappa III. Anti-Pr with Vkappa IV subgroup light chains exclusively recognized alpha 2,3-linked N-acetylneuraminic acid.
  
  
  CONCLUSIONS
  Including data from the literature, the repertoire of the light-chain variable domain in pathological anti-Pr cold agglutinins exhibits a clear bias towards the use of the single germline gene-derived subgroup, Vkappa IV (eight of 17 or 47%). The association of Vkappa IV subgroup light chain-containing anti-Pr cold agglutinins with binding to alpha 2,3-, but not alpha 2,6-linked N-acetyneuraminic acid raises speculations about a possible role of subgroup-derived determinants in anti-Pr binding.
authors.affiliation: Institute for Immunology, Blood Bank, University of Heidelberg Medical Center, Heidelberg, Germany. Albrecht_Leo@med.uni-heidelberg.de
authors.forename: A
authors.initials: A
authors.lastname: Leo
authors.forename: H
authors.initials: H
authors.lastname: Kreft
authors.forename: H
authors.initials: H
authors.lastname: Hack
authors.forename: T
authors.initials: T
authors.lastname: Kempf
authors.forename: D
authors.initials: D
authors.lastname: Roelcke
mesh_terms: D000328:Adult; D000373:Agglutinins / Q000276:immunology*; D000744:Anemia, Hemolytic, Autoimmune / Q000276:immunology*; D000918:Antibody Specificity; D001789:Blood Group Antigens / Q000737:chemistry / Q000276:immunology*; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D003450:Cryoglobulins; D006021:Glycophorins / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D007147:Immunoglobulin Light Chains / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000276:immunology; D007145:Immunoglobulin kappa-Chains / Q000276:immunology; D008969:Molecular Sequence Data; D015394:Molecular Structure; D019158:N-Acetylneuraminic Acid / Q000276:immunology
chemical_list: D000373:Agglutinins; D001789:Blood Group Antigens; D003450:Cryoglobulins; D006021:Glycophorins; D016056:Immunodominant Epitopes; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; C493795:Pr antigen, human; C029443:cold agglutinins; D019158:N-Acetylneuraminic Acid