Sickle cell leg ulcers are associated with HLA-B35 and Cw4

We determined the HLA-A, B, C, and DR types in nine patients with sickle cell anemia (SS) who had leg ulcers or a history of leg ulcers, and in 29 control patients with SS without leg ulcers. Six (67%) of the nine patients with leg ulcers had HLA-B35 and each of these six patients also had HLA-Cw4. In contrast, only eight (28%) of the 29 control patients with SS had HLA-B35 and only three (10%) of these patients had both HLA-B35 and Cw4. The relative risk for development of leg ulcers in patients with SS who had both HLA-B35 and Cw4 was 17 times greater than that of patients without these antigens or who had only one antigen. The frequency of HLA-B35 was also significantly higher in patients with SS and leg ulcers than in a reference population (31%) consisting of 68 healthy black persons. These results suggest that genetic factors or an HLA-related altered immune response may contribute to the development of leg ulcers in sickle cell anemia.