Autoantibodies to hair follicles in C3H/HeJ mice with alopecia areata-like hair loss

We have previously described spontaneous but reversible hair loss that clinically and histologically resembles human alopecia areata in a colony of C3H/HeJ mice. Alopecia areata in humans is associated with antibodies to hair follicles. This study was conducted to determine whether C3H/HeJ mice with hair loss have a similar abnormal antibody response to hair follicles. Eighteen C3H/HeJ mice with alopecia, 12 unaffected littermates, and 15 control mice were examined for circulating antibodies to C3H/HeJ anagen hair follicles by indirect immunofluorescence and against extracts of isolated C3H/HeJ and human anagen hair follicles by immunoblotting. Using both procedures, antibodies to anagen hair follicles were present in all C3H/HeJ mice with alopecia but in none of the control mice. The antibodies were also present in some unaffected C3H/HeJ littermates but were absent in mice of an unrelated strain with inflammatory skin disease and alopecia, indicating that their appearance did not result from the hair loss. These antibodies reacted to hair follicle-specific antigens of 40-60 kDa present in murine and human anagen hair follicles. These antigens were also reactive with human alopecia areata antibodies. Some of the antibodies in both C3H/HeJ mice and humans with alopecia areata reacted to antigens of 44 and 46 kDa, which were identified as hair follicle-specific keratins. This study indicates that C3H/HeJ mice with hair loss have circulating antibodies to hair follicles similar to those present in humans with alopecia areata. These findings confirm that these mice are an appropriate model for human alopecia areata and support the hypothesis that alopecia areata results from an abnormal autoimmune response to hair follicles.