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Background: While RBC antigen frequencies for whites of Northern European ancestry are known, the relative frequencies of RBC antibodies within this population have not been determined. The distribution of RBC alloantibodies by sex and age was studied, as were the immunogenicity of RBC antigens and the occurrence of RBC alloantibody clusters in a geographically defined population.Study Design and Methods: RBC alloimmunization among patients and donors in Olmsted County, MN, was determined for the period from 1975 to 1995. Alloantibody frequencies were used to calculate the potency of each antigen relative to K. Cluster analysis was applied to the data to identify natural groupings of antibodies.Results: The frequency and potency of 33 alloantibodies from 1345 alloimmunized subjects were estimated. The most frequent alloantibodies were E (20.8%), Le(a) (18.6%), K (14.7%), D (12.9%), Le(b) (9.4%), M (7.2%), P(1) (6.7%), Fy(a) (6.3%), C (6.8%), and c (3.5%). The most potent antigens were Wr(a) (0.363), C(w) (0.078), Le(a) (0.03), E (0.028), V (0.025), Js(a) (0.023), Kp(b) (0.023), Go(a) (0.023), JMH (0.023), and Rd (0.023). Greater frequency of overall alloimmunization (M:F = 1:2.7), anti-D (p<0.0001), and anti-Le(a) (p = 0.003) was seen among females. Warm autoantibodies were more frequent among males with positive antibody screens (p<0.0001). No other gender differences were observed. Alloimmunization increased with age for K, Kp(a), Fy(a), D, C, E, and warm autoantibodies. Frequencies of alloimmunization to Le(a), Le(b), M, and P(1) decreased with age. The cluster analysis showed grouping of the antibodies to C and D as well as to Le(a) and Le(b), but the other RBC alloantibodies did not form clusters.Conclusion: Less than 1 percent of residents tested had positive antibody screens. Anti-E and anti-Le(a) were more common than anti-K. Wr(a) and C(w) were more potent antigens than K. Most antibodies showed an increase in frequency with increasing age. Except for anti-C and -D and anti-Le(a) and -Le(b), RBC alloantibodies did not occur in clusters. [ABSTRACT FROM AUTHOR]