Thyroid peroxidase DNA immunization replicates thyroid autoimmunity.

2004 NOV 3 - (NewsRx.com & NewsRx.net) -- Thyroid peroxidase DNA is superior to protein immunization in replicating human thyroid autoimmunity in HLA-DRB1*0301 (DR3) transgenic mice.

"Murine experimental autoimmune thyroiditis (EAT), characterized by thyroid destruction after immunization with thyroglobulin (Tg), has long been a useful model of organ-specific autoimmune disease. More recently, porcine thyroid peroxidase (pTPO) has also been shown to induce thyroiditis, but these results have not been confirmed. When (C57BL/6 x CBA)F[subscript]1mice, recently shown to be susceptible to mouse TPO-induced EAT, were immunized with plasmid DNA to human TPO (hTPO) and cytokines IL-12 or GM-CSF, significant antibody titers were generated, but minimal thyroiditis was detected in one mouse only from the TPO + GM-CSF immunized group," scientists in the United States, England, and Poland report.

"However, after TPO DNA immunization of HLA-DR3 transgenic class II-deficient NOD mice, thyroiditis was present in 23% of mice injected with TPO + IL-12 or GM-CSF," stated Jeffrey C. Flynn at Wayne State University in the U.S. and collaborators in the U.S., England, and Poland. "We also used another marker for assessing the closeness of the model to human thyroid autoimmunity by examining the epitope profile of the anti-TPO antibodies to immunodominant determinants on TPO. Remarkably, the majority of the anti-TPO Abs was directed to immunodominant regions A and B, demonstrating the close replication of the model to human autoimmunity."

"TPO protein immunizations of HLA-DR3 transgenic mice with recombinant hTPO ...