RESTRICTED IMMUNOGLOBULIN V-H REGION REPERTOIRE IN CHRONIC LYMPHOCYTIC-LEUKEMIA PATIENTS WITH AUTOIMMUNE HEMOLYTIC-ANEMIA

Between 10% and 25% of chronic lymphocytic leukemia (CLL) patients hav e episodes of autoimmune hemolytic anemia (AIHA) during the course of their disease, The anti-erythrocyte autoantibodies in most cases are p olyclonal and express a different heavy chain isotype than the maligna nt clone, indicating that they are secreted by normal autoreactive B l ymphocytes. To further investigate the pathogenesis of the AIHA in CLL , we analyzed the Ig heavy (H) chain variable region genes expressed b y leukemic cells from CLL patients with and without AIHA. Two V-H gene s were preferentially expressed by the leukemic cells in the CLL cases with AIHA and were present in 9 of the 12 investigated cases. The 51p 1/DP-10 gene was expressed in 5 of these cases and was absent in the c ontrol group of 12 consecutive CLL cases without AIHA, whereas the DP- 50 gene was present in 4 CLL-AIHA cases and only once in the control C LL group, A strikingly similar H-chain CDR3 region that contained a si ngle reading frame of the DXP4 D-H gene segment, an N-encoded proline at the D-H/J(H) boundary, end a tyrosine-rich region encoded by the J( H)6 gene segment was observed in four CLL-AIHA cases. The preferential expression of two V-H gene segments and a particular CDR3 region by t he leukemic cells of patients with AIHA suggests that the antibodies p roduced by the CLL cells are directly involved in the pathogenesis of the hemolytic anemia. (C) 1996 by The American Society of Hematology.