Yukiko Izumi

Characteristics of experimental autoimmune hypophysitis in rats : Major antigens are growth hormone, thyrotropin, and luteinizing hormone in this model

We produced experim entalautoimmune hypophysitis (EAH) in rats and investi gated its characteristics. Female Lewis rats were immunized by two injections with homologous pituitary homogenate and complete Freund’s adjuvant. Blood was coll ected seri ally from the rats, and serum antibodies to pituitary antigens were examined . The rats were sacrificed 2 or 4 weeks after the final immunization, and hi stological examinations of the endocrineorgans were carried out. Hi stolog ical examination revealedslight , focal infiltration of mononuclearcells in the pituitary gland only in the rats immunized with the pituitary homogenate. Infiltration of mononuclearcells was not observed in the thyroidgland , pancreas, adrenal gland , or ovary. In the serological examination, antibodies to bothcytoso licantigens and cytoplas micparticle a nti gens from the pituitaryg land were detected by enzyme- linked immunosorbent assay (ELISA), and these antibody levels increased with time. We stern blottingusing the sennn antibodiesidentified an immunoreactive protein of -2 1.5 k.Daamo ng these antigens, and we confirmed that this protein was ratgrow thhormone (GH). Furth ermore, antibodies to GH, thyrotropin (TSH), and luteinizing hormone (LH) were detected by E LISA. Antibodies to folli cule stimulating horm one, prol actin , or adrenocorticotropin were not detected . These data suggest that several antigens from the pituitary gland are involved in EAH inrats, and that GH, TSH, and LH are major antigens among the pituitary antigens in this model.

Blocking‐type anti‐TSH receptor antibodies and relation to responsiveness to antithyroid drug therapy and remission in Graves’ disease

objective Antithyroid drugs are effective in some patients with Graves’ disease but not in others. The factors responsible for this difference are still unknown. We examined the relationship between the nature of anti‐TSH receptor (TSH‐R) antibodies and responsiveness to drugs in Graves’ disease.

Development of liver dysfunction after delivery is possibly due to postpartum autoimmune hepatitis. A report of three cases

Autoimmune diseases, especially autoimmune thyroid disease, frequently develop after delivery due to the immune rebound mechanism. Most cases involve transient dysfunction of affected organs. Weexamined three patients who developed liver dysfunction after delivery. They were all diagnosed with definite or probable autoimmune hepatitis using the scoring system of the International Autoimmune Hepatitis Group. Moreover, all of them had anti‐CYP2D6 antibodies detected by a sensitive radioligand assay. Our findings strongly suggest that liver dysfunction is induced by postpartum autoimmune hepatitis, and clinicians should be aware of this disease.

Anti-CYP2D6 antibodies detected by quantitative radioligand assay and relation to antibodies to liver-specific arginase in patients with autoimmune hepatitis.

BACKGROUND Antibodies to cytochrome P4502D6 (CYP2D6) were measured and their prevalence compared with that of antibodies to liver-specific arginase in patients with autoimmune hepatitis (AIH). METHODS Anti-CYP2D6 antibodies were measured by sensitive radioligand assay and enzyme-linked immunosorbent assay (ELISA), and anti-arginase antibodies were measured by ELISA in 132 patients (definite AIH 11, probable AIH 36, hepatitis C 20, hepatitis B 23, other autoimmune diseases 42) and 50 healthy controls. RESULTS CYP2D6 index (radioligand assay) was significantly higher in all groups of patients than those in healthy controls. A higher index than the cut-off value (mean+3 S.D. in healthy controls) was found in 36.4%, 44.4%, 25.0%, 17.4% and 28.6% of patients with definite AIH, probable AIH, hepatitis C, hepatitis B and other autoimmune diseases, respectively. CYP2D6 index was not related to serum IgG, anti-nuclear antibody or AIH scores, and was weakly correlated with anti-arginase antibody activity. When CYP2D6 index and anti-arginase antibodies were combined, 55.3% of AIH patients were positive for either one or both antibodies. CONCLUSIONS Anti-CYP2D6 antibodies by radioligand assay were frequently present in patients with AIH. Combined tests for anti-CYP2D6 radioligand assay and anti-arginase antibodies resulted in detection of 55% of AIH patients.

Relation between post-partum liver dysfunction and anti-cytochrome 2D6 antibodies.

Problem:  Autoimmune thyroid disease frequently aggravates or develops after delivery through the immune rebound mechanism. However, little is known about the post‐partum development of autoimmune hepatitis (AIH).