Iodine content of thyroglobulin in NOD.H2h4 mice developing iodine-accelerated autoimmune thyroiditis

OBJECTIVE: In NOD.H2h4 mice, high dietary iodine intake has been known to cause Iodineaccelerated Spontaneous Autoimmune Thyroiditis (ISAT) via an unknown mechanism. The aim of the study was to examine whether the NOD.H2h4 genetic background predisposes to enhanced iodine organification in thyroglobulin (Tg), a target autoantigen in ISAT. DESIGN: To avoid issues associated with an ongoing anti-Tg antibody response, we assessed Tg iodination levels in iodine-fed, B-cell deficient NOD.H2h4 mice. Additionally, we tested whether humoral or cellular immune responses of iodine-fed NOD.H2h4 mice are preferentially directed to Tg with increased iodine content (I-Tg) or known pathogenic Tg peptides that contained iodine. RESULTS: The iodine content of Tg was not significantly different between control (9.0±2.7 I atoms per monomer) and iodine-fed mice (10.9±0.3 I atoms per monomer). Furthermore, in iodine-fed NOD.H2h4 mice developing ISAT, strong but equivalent serum IgG responses were detected to both Tg or I-Tg, whereas their lymphoid cells were stimulated weakly but equally well by Tg or I-Tg in vitro and did not show reactivity against a panel of five pathogenic Tg peptides that contained iodine. CONCLUSIONS: The results suggest that development of ISAT in NOD.H2h4 mice is not associated with enhanced iodine organification or differential B- or T-cell responses to iodinated determinants in Tg.