Murine autoimmune hemolytic anemia induced via xenogeneic erythrocyte immunization: III. Influences of sex

Abstract

Mice immunized with xenogeneic rat erythrocytes develop erythrocyte autoantibodies and a hemolytic anemia. To investigate the possibility of a sex dimorphism in this response, male and female N:NIH(S), C3H, C57BL/6, C3B6 F 1, BALB/c, CBA/Hn, NZW, NZB, and NZB/W F 1 strains of mice were immunized with rat red blood cells (Rrbc). The number of mice that developed erythrocyte autoantibodies, the time of onset of this response, the direct antiglobulin titer, the class and subclass of the erythrocyte-bound autoantibody, and the severity of anemia and titer of anti-Rrbc antibody were determined. Further, to examine the influence of sex hormones, gonadectomy and opposite sex hormone treatments were performed on male and female N:NIH(S) mice. In five of seven responding strains, a higher frequency of female mice developed erythrocyte autoantibodies than male mice. Female mice also demonstrated a more rapid onset, requiring fewer Rrbc injections, accompanied by a more severe anemia. Erythrocyte-bound autoantibodies of IgG 1, IgG 2a, IgG 2b, and IgM specificities were present to a greater degree in female mice than in male mice, and an enhanced female anti-Rrbc hemagglutinin response was also observed. Moreover, gonadectomy and opposite sex hormone therapy abolished the observed sex differences in respect to autoantibody formation and anti-Rrbc response. Finally, the possibility of an X-chromosome linked mechanism was not indicated.