Restriction in the repertoire of the immunoglobulin light chain subgroup in pathological cold agglutinins with anti‐Pr specificity

Background and Objectives  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‐Pr1–3 subclassification and immunodominant sialic acid, light chains in 13 anti‐Pr cold agglutinins were investigated.

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