Cellular thyroid peroxidase (TPO), unlike purified TPO and adjuvant, induces antibodies in mice that resemble autoantibodies in human autoimmune thyroid disease
Jc. Jaume et al., Cellular thyroid peroxidase (TPO), unlike purified TPO and adjuvant, induces antibodies in mice that resemble autoantibodies in human autoimmune thyroid disease, J CLIN END, 84(5), 1999, pp. 1651-1657
Autoantibodies to several protein antigens in human autoimmunity interact w
ith a restricted range of epitopes, whereas diverse epitopes are recognized
by antibodies induced in animals using antigen and adjuvant. To examine th
e basis for this difference, we compared the qualitative nature of antibodi
es developing in AKR/N mice injected with purified thyroid peroxidase (TPO)
and adjuvant or with TPO expressed on major histocompatibility complex (NM
C) class II+ fibroblasts. Mice injected with purified TPO had higher TPO an
tibody levels than TPO+/class II+ fibroblast-treated mice. Despite lower ti
ters, recipients of TPO+/class II+ cells developed very high affinity antib
odies (K-d = similar to 10(-10) M), comparable with those of human TPO auto
antibodies and about 10-fold higher than those in purified TPO plus adjuvan
t-immunized mice, Moreover, more than 90% of TPO antibodies in TPO+/class I
I+ fibroblast-injected mice, compared with only approximately 50% in TPO pl
us adjuvant-immunized mice, were to the immunodominant region recognized by
patients' autoantibodies. Consistent with this epitopic restriction, TPO+/
class II+ fibroblast-injected mice had TPO antibody epitopic fingerprints s
imilar to those of human autoantibodies.
In conclusion, mice injected with TPO+/class II+ fibroblasts, but not those
injected with purified TPO and adjuvant, develop antibodies closely resemb
ling autoantibodies in human disease. These observations indicate that some
animal models based on conventional immunization may not be representative
of human diseases with a major humoral component.