Autoimmune Response to the Thyroid in Humans: Thyroid Peroxidase-The Common Autoantigenic Denominator

  title={Autoimmune Response to the Thyroid in Humans: Thyroid Peroxidase-The Common Autoantigenic Denominator},
  author={Sandra M. McLachlan and Basil Rapoport},
  journal={International Reviews of Immunology},
  pages={587 - 618}
Autoimmunity to thyroid peroxidase (TPO), manifest as high affinity IgG class auto-antibodies, is the common denominator of human thyroid autoimmunity, encompassing patients with overt hyper-or hypothyroidism as well as euthyroid individuals with subclinical disease. The identification and cloning of TPO (the “thyroid microsomal antigen”) provided the critical tool for analyzing B and T cell reactivity to this major thyroid autoantigen. In particular, the availability of immunoreactive TPO… 

Thyroid peroxidase as an autoantigen.

Overall, some TPO-specific T cells and the majority of autoantibodies in humans develop in response to TPO presented by thyroid cells, rather than to T PO released by damaged thyrocytes.

Human monoclonal thyroglobulin autoantibodies: epitopes and immunoglobulin genes.

The TgAb panel provides novel information regarding the repertoire of H chain genes encoding human TgAbs as well as the relationship between the H chains and the epitopes recognized on this major thyroid autoantigen.

The human anti-thyroid peroxidase autoantibody repertoire in Graves' and Hashimoto's autoimmune thyroid diseases

There is only limited amino acid replacement in most of the TPO-specific light chains, particularly in those encoded by J proximal IGLV or IGKV genes, suggesting that a defect in receptor editing can occur during aAb generation in AITD.

Human monoclonal autoantibodies to B-cell epitopes outside the thyroid peroxidase autoantibody immunodominant region.

The first insight into the immunoglobulin genes, affinities and epitopes of human monoclonal autoantibodies that bind outside the TPO-immunodominant region is provided.

Localization of the immunodominant region on human thyroid peroxidase in autoimmune thyroid diseases: an update

The aim of the present review is to summarize the current knowledge regarding the localization of the immunodominant region recognized by human thyroid peroxidase-specific autoantibodies generated during the development of autoimmune thyroid diseases.

Induction of autoimmune thyroiditis and hypothyroidism by immunization of immunoactive T cell epitope of thyroid peroxidase.

It is demonstrated that TPO is the autoantigen for the development of lymphocyte thyroiditis and thyroid dysfunction, and peptide 540-559 is the immunodominant T cell epitope of TPO.

Search for the Autoantibody Immunodominant Region on Thyroid Peroxidase: Epitopic Footprinting with a Human Monoclonal Autoantibody Locates a Facet on the Native Antigen Containing a Highly Conformational Epitope1

A footprinting approach is used that can localize a highly conformational, discontinuous epitope on a very large molecule and provides the basis for rational guided mutagenesis studies to more fully characterize the TPO immunodominant region.

Why measure thyroglobulin autoantibodies rather than thyroid peroxidase autoantibodies?

TgAb epitopes could distinguish between individuals who are euthyroid or who have clinical disease, and it is conceivable that Tg polymorphisms, combined with the explosive mix of iodine, TPO and H2O2 necessary for thyroid hormone synthesis, inadvertently provide the trigger for the autoimmune thyroid response.

Thyroid peroxidase autoantibodies in euthyroid subjects.

Autoantibody profiling of patients with autoimmune thyroid disease using a new multiplexed immunoassay method

The use of only the TPOAb test does not guarantee sufficient diagnostic sensitivity, and knowledge of the autoantibody profile could allow the identification of sub-groups of patients with a different degree of activation of the thyroid autoimmune process.



Genetic and epitopic analysis of thyroid peroxidase (TPO) autoantibodies: markers of the human thyroid autoimmune response

Monoclonal human TPOautoantibodies will be invaluable for B cell presentation of TPO to determine the T cell epitopes involved in TPO autoantibody production, and evidence for conservation as well as inheritance of the fingerprints in some families may provide insight into the genetic basis of human autoimmune thyroid disease.

Recognition by recombinant autoimmune thyroid disease-derived Fab fragments of a dominant conformational epitope on human thyroid peroxidase.

To characterize the nature of thyroid peroxidase (TPO) autoantibodies present in the sera of patients with autoimmune thyroid disease, we cloned three IgG1/kappa Fab fragments which bind 125I-TPO.

Thyroid peroxidase autoantibody fingerprints in hypothyroid and euthyroid individuals. I. Cross-sectional study in elderly women.

No difference in TPOAutoantibody epitopes was observed in this cross-sectional study of hypothyroid and euthyroid individuals, demonstrating that the majority of TPO autoantibodies in both groups recognize the TPO immunodominant domain.

Rarity of autoantibodies to a major autoantigen, thyroid peroxidase, that interact with denatured antigen or with epitopes outside the immunodominant region

The findings demonstrate the bias of the human B cell repertoire towards recognition of an immunodominant region on the conformationally intact form of a major thyroid autoantigen.

Thyroid peroxidase autoantibodies of IgE class in thyroid autoimmunity.

IgE class TPO autoantibodies were present in 13 of 18 Graves' and in 12 of 17 Hashimoto patients (sera diluted 1/6) and their presence strengthens the link between autoimmune thyroid disease and immune responses involving TH2 cells.

Human organ-specific autoimmune disease. Molecular cloning and expression of an autoantibody gene repertoire for a major autoantigen reveals an antigenic immunodominant region and restricted immunoglobulin gene usage in the target organ.

The molecular cloning of the genes for 30 high-affinity, IgG-class human autoantibodies to TPO from thyroid-infiltrating B cells suggests that there is restriction in H and L chain usage in relation to the interaction with specific antigenic domains in human, organ-specific autoimmune disease.

Detection Of Autoantibodies To Recombinant Human Thyroid Peroxidase By Sensitive Enzyme Immunoassay

There appeared to be no difference in the affinity of high titre human anti-TPO for recombinant and natural‐TPO antigen with both ELISAs able to detect 0.05 U/ml of anti‐ TPO activity (reference preparation NIBSC 66/387).

Recombinant thyroid peroxidase autoantibodies can be used for epitopic "fingerprinting" of thyroid peroxidase autoantibodies in the sera of individual patients.

The present study on a large sample of sera with TPO autoantibodies indicates that by using TPO-specific F(ab) selected to cover all regions of the TPO immunodominant region, it is possible to obtain a TPO epitopic fingerprint for each serum.

Determination at the molecular level of a B-cell epitope on thyroid peroxidase likely to be associated with autoimmune thyroid disease.

Determination of the nucleotide sequences of 18 clones recognized by monoclonal antibody 47 localized its epitope to 9 amino acids in the human TPO protein, indicating that the major part of the epitope is represented by a continuous portion of the TPO sequence.