Thyroid peroxidase/microsomal antibodies are not identical with thyroid cytotoxic antibodies in autoimmune thyroiditis

1990 ◽  
Vol 123 (4) ◽  
pp. 431-437 ◽  
Author(s):  
Ulrich Bogner ◽  
Peter Kotulla ◽  
Harm Peters ◽  
Horst Schleusener
Keyword(s):  
Cytotoxic Activity ◽  
Hashimoto’S Thyroiditis ◽  
Cytotoxicity Assay ◽  
Human Thyroid ◽  
Hashimoto's Thyroiditis ◽  
Thyroid Peroxidase ◽  
Specific Lysis ◽  
Thyroid Peroxidase Antibody ◽  
Microsomal Antibody ◽  
Dependent Cell

Abstract. Cytotoxic activity in sera of patients with Hashimoto's thyroiditis was measured with an antibody-dependent cell-mediated cytotoxicity assay. Cytotoxicity was determined in a 51chromium release assay using human thyroid cell targets incubated with heat-inactivated serum or IgG from patients with Hashimoto's thyroiditis. Effector cells were obtained from peripheral mononuclear cells of normal subjects. Cytotoxicity was significantly increased in patients with Hashimoto's thyroiditis (median specific lysis 20.2%, range 2.1-58.8) compared with normals (median specific lysis 8.1%, range 0-19.5; p<0.00001). The amount of percent specific lysis did not correlate with the titres of microsomal antibodies determined by different methods: passive hemagglutination technique (r=0.2), enzyme immunoassay with microsomal antigen (r=0.16), and radioimmunoassay for thyroid peroxidase antibody (r=0.02). The cytotoxic activity was located in the IgG fraction, both in microsomal antibody positive and negative sera. After pre-incubation of microsomal antibody/thyroid peroxidase antibody positive or negative sera with purified thyroid peroxidase followed by analysis in the antibody-dependent cell-mediated cytotoxicity assay, cytotoxicity decreased in only 2 cases but was unchanged in the remaining sera. Western blot experiments with solubilized thyroid membranes and immunoblotting with cytotoxic-positive/microsomal antibody negative sera showed no binding to thyroid peroxidase. Our data suggest that cytotoxicity in sera from patients with Hashimoto's thyroiditis is not mediated by antibodies against thyroid peroxidase, but by antibodies not yet identified.

scholarly journals Antibodies to Thyroid Peroxidase Arise Spontaneously with Age in NOD.H-2h4 Mice and Appear after Thyroglobulin Antibodies

2010 ◽  
Vol 31 (4) ◽  
pp. 600-600
Author(s):  
Chun-Rong Chen ◽  
Sepehr Hamidi ◽  
Helen Braley-Mullen ◽  
Yuji Nagayama ◽  
Catherine Bresee ◽  
...  
Keyword(s):  
Hashimoto’S Thyroiditis ◽  
Time Course ◽  
Thyroid Autoimmunity ◽  
Cross Reactivity ◽  
Eukaryotic Cells ◽  
Human Thyroid ◽  
Hashimoto's Thyroiditis ◽  
Thyroid Peroxidase ◽  
Thyroglobulin Antibodies ◽  
Self Tolerance

Abstract Hashimoto’s thyroiditis, a common autoimmune disease, is associated with autoantibodies to thyroglobulin (Tg) and thyroid peroxidase (TPO). TPO, unlike abundant and easily purified Tg, is rarely investigated as an autoantigen in animals. We asked whether antibodies (Abs) develop to both TPO and Tg in thyroiditis in mice that is induced (C57BL/6 and DBA/1 strains) or arises spontaneously (NOD.H-2h4). Screening for TPOAbs was performed by flow cytometry using mouse TPO-expressing eukaryotic cells. Sera were also tested for binding to purified mouse Tg and human TPO. The antibody data were compared with the extent of thyroiditis. Immunization with mouse TPO adenovirus broke self-tolerance to this protein in C57BL/6 mice, but thyroiditis was minimal and TgAbs were absent. In DBA/1 mice with extensive granulomatous thyroiditis induced by Tg immunization, TPOAbs were virtually absent despite high levels of TgAbs. In contrast, antibodies to mouse TPO, with minimal cross-reactivity with human TPO, arose spontaneously in older (7–12 months) NOD.H-2h4 mice. Unexpectedly, TgAbs preceded TPOAbs, a time course paralleled in relatives of probands with juvenile Hashimoto’s thyroiditis. These findings demonstrate a novel aspect of murine and human thyroid autoimmunity, namely breaking B cell self-tolerance occurs first for Tg and subsequently for TPO.

Inhibition by immunoglobulin G of synthesis of thyroid hormone in thyroid cultures from hypothyroid patients with goitrous Hashimoto's thyroiditis

1990 ◽  
Vol 123 (5) ◽  
pp. 511-518 ◽  
Author(s):  
Jaeduk Noh ◽  
Noboru Hamada ◽  
Hifumi Saito ◽  
Midori Yoshimoto ◽  
Hiroyuki Iwasaki ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Peroxidase Activity ◽  
Immunoglobulin G ◽  
Hashimoto’S Thyroiditis ◽  
Thyroid Tissue ◽  
Hashimoto's Thyroiditis ◽  
Thyroid Peroxidase ◽  
Hormone Synthesis ◽  
Microsomal Antibody ◽  
Hypothyroid Patients

Abstract. Recently, thyroid microsomal antigen was identified as thyroid peroxidase, and thyroid microsomal antibody was found to inhibit thyroid peroxidase activity in vitro. We investigated the possibility that anti-microsomal antibody inhibits the iodination of tyrosine, in vivo. Immunoglobulin G with or without anti-microsomal antibody from hypothyroid patients with goitrous Hashimoto's thyroiditis inhibited thyroid hormone synthesis in cultured slices of normal human thyroid tissue. IgGs with anti-microsomal antibody inhibited 125I thyroidal uptake and thyroid hormone synthesis stimulated by TSH more than normal IgG did. However, the same results were obtained with IgGs without anti-microsomal antibody. This effect did not involve anti-microsomal antibody, anti-thyroglobulin antibody, TSH-binding inhibitor immunoglobulin, thyroid stimulation-blocking immunoglobulin, or the cAMP level of the thyroid tissue. The ratio of organic I to inorganic I with stimulation by TSH in slices incubated with IgG from hypothyroid patients with goitrous Hashimoto's thyroiditis or normal IgG was not significantly different, but was significantly higher in slices incubated with methylmercaptoimidazole. Therefore, IgG from hypothyroid patients with goitrous Hashimoto's thyroiditis mainly suppressed 125I thyroidal uptake, rather than inhibiting thyroid peroxidase activity. In addition, this IgG was present in the serum of 11 of the 12 hypothyroid patients with Hashimoto's thyroiditis studied. This IgG may be involved in the mechanism that causes hypothyroidism in some patients with goitrous Hashimoto's disease.

Challenging diagnosis of thyroid hormone resistance initially as Hashimoto’s thyroiditis

2019 ◽  
Vol 32 (2) ◽  
pp. 203-206 ◽  
Author(s):  
Tong Wooi Ch’ng ◽  
Vivian L. Chin
Keyword(s):  
Thyroid Hormone ◽  
Hashimoto’S Thyroiditis ◽  
Hashimoto's Thyroiditis ◽  
Heterozygous Mutation ◽  
Thyroid Peroxidase ◽  
Thyroid Function Tests ◽  
Resistance To Thyroid Hormone ◽  
Hyperactivity Disorder ◽  
Thyroid Peroxidase Antibody ◽  
High Index Of Suspicion

Abstract Background Resistance to thyroid hormone (RTH) commonly presents with goiter, attention deficit hyperactivity disorder (ADHD), short stature and tachycardia. However, due to its variable presentation with subtle clinical features, a third of the cases are mistreated, typically as hyperthyroidism. Case presentation A 15-year-old female with ADHD and oligomenorrhea was initially diagnosed as Hashimoto’s thyroiditis but found to have a rare heterozygous mutation in c803 C>G (p Ala 268 Gly) in the THRβ gene, confirming resistance to thyroid hormone. Conclusions Fluctuating thyroid function tests in addition to thyroid peroxidase antibody (TPO Ab) positivity complicated the diagnosis of RTH, initially diagnosed as Hashimoto’s thyroiditis. A high index of suspicion is needed to prevent misdiagnosis and mistreatment.

scholarly journals Antibodies to Thyroid Peroxidase Arise Spontaneously with Age in NOD.H-2h4 Mice and Appear after Thyroglobulin Antibodies

Endocrinology ◽  
2010 ◽  
Vol 151 (9) ◽  
pp. 4583-4593 ◽  
Author(s):  
Chun-Rong Chen ◽  
Sepehr Hamidi ◽  
Helen Braley-Mullen ◽  
Yuji Nagayama ◽  
Catherine Bresee ◽  
...  
Keyword(s):  
Hashimoto’S Thyroiditis ◽  
Time Course ◽  
Thyroid Autoimmunity ◽  
Cross Reactivity ◽  
Eukaryotic Cells ◽  
Human Thyroid ◽  
Hashimoto's Thyroiditis ◽  
Thyroid Peroxidase ◽  
Thyroglobulin Antibodies ◽  
Self Tolerance

Hashimoto’s thyroiditis, a common autoimmune disease, is associated with autoantibodies to thyroglobulin (Tg) and thyroid peroxidase (TPO). TPO, unlike abundant and easily purified Tg, is rarely investigated as an autoantigen in animals. We asked whether antibodies (Abs) develop to both TPO and Tg in thyroiditis that is induced (C57BL/6 and DBA/1 mice) or arises spontaneously (NOD.H-2h4 mice). Screening for TPOAbs was performed by flow cytometry using mouse TPO-expressing eukaryotic cells. Sera were also tested for binding to purified mouse Tg and human TPO. The antibody data were compared with the extent of thyroiditis. Immunization with mouse TPO adenovirus broke self-tolerance to this protein in C57BL/6 mice, but thyroiditis was minimal and TgAbs were absent. In DBA/1 mice with extensive granulomatous thyroiditis induced by Tg immunization, TPOAbs were virtually absent despite high levels of TgAbs. In contrast, antibodies to mouse TPO, with minimal cross-reactivity with human TPO, arose spontaneously in older (7–12 months) NOD.H-2h4 mice. Unexpectedly, TgAbs preceded TPOAbs, a time course paralleled in relatives of probands with juvenile Hashimoto’s thyroiditis. These findings demonstrate a novel aspect of murine and human thyroid autoimmunity, namely breaking B cell self-tolerance occurs first for Tg and subsequently for TPO.

Sign in / Sign up

Export Citation Format

Share Document