Recombinant thyroid antigens: preparation and application in the diagnosis and treatment of autoimmune diseases

Vrač skoroj pomoŝi (Emergency Doctor) ◽

10.33920/med-02-2102-05 ◽

2021 ◽

pp. 48-53

Author(s):

Alexander Vladimirovich Zubkov

Keyword(s):

Autoimmune Diseases ◽

Hormone Receptor ◽

Extracellular Domain ◽

Thyroid Stimulating Hormone ◽

Human Thyroid ◽

Antigenic Structure ◽

Thyroid Peroxidase ◽

Α Subunit ◽

Thyroid Autoantigens ◽

Stimulating Hormone

New opportunities are opening up in the study of the relationship between the antigenic structure of thyroid autoantigens and autoantibodies in the pathogenesis of such autoimmune diseases as Graves’ disease (GD) and autoimmune thyroiditis (AIT) using synthesized recombinant proteins of the thyroid-stimulating hormone receptor (TSHR) and human thyroid peroxidase (TPO). In the present work, the results of cloning of the fragments of the TPO extracellular domain and fragments of the RNA sequence of the α-subunit of TSHR, which do not contain nucleotide substitutions, are demonstrated. Recombinant vectors for the expression of proteins of the α-subunit of thyroid-stimulating hormone receptor and fragments of the TPO extracellular domain have been obtained.

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The Antibody Response in Human Autoimmune Thyroid Disease

Clinical Science ◽

10.1042/cs0920529 ◽

1997 ◽

Vol 92 (6) ◽

pp. 529-541 ◽

Cited By ~ 22

Author(s):

Richard S. McIntosh ◽

M. Suhail Asghar ◽

Anthony P. Weetman

Keyword(s):

Antibody Response ◽

Thyroid Disease ◽

Hormone Receptor ◽

Autoimmune Thyroid Disease ◽

Thyroid Stimulating Hormone ◽

Thyroid Peroxidase ◽

Autoimmune Thyroid ◽

Thyroid Autoantigens ◽

Reactive Antibody ◽

Stimulating Hormone

1. The analysis of the antibody response in autoimmune thyroid disease has followed several historical trends. It was the investigation of thyroid-reactive antibody that allowed the initial characterization of the three principle thyroid autoantigens, thyroglobulin, thyroid peroxidase and the thyroid stimulating hormone receptor. 2. Analysis can be grouped under two broad areas: analysis of the physiological and pathological effects of the antibody, and analysis of the structure of the antibodies themselves. This review will focus on the latter. 3. Within recent years there has been a great increase in knowledge of thyroid-reactive antibody structure, principally through the adoption of phage display combinatorial library methodologies. While this latter technique has established some general principles for antibodies to thyroglobin and especially thyroid peroxidase, there is still a substantial gap in our knowledge of the antibody response to the thyroid stimulating hormone receptor. 4. Thyroid peroxidase antibodies have a relatively restricted V-region usage, and there is a correlation between the V-regions used and the epitope on thyroid peroxidase bound. In particular the Vκ light chain, Vκl(O12), is associated with reactivity to one epitope. 5. The purpose of this review is to bring together the latest results concerning the molecular analysis of the antibody response in autoimmune thyroid disease, to highlight areas of ignorance and conflict, and to discuss the methods adopted to circumvent the problems associated with analysis of the antibody response.

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Hipotiroidismo Associado a Anticorpos Anti-Receptor da Hormona TSH com Ação Bloqueadora Determinada In Vitro

Acta Médica Portuguesa ◽

10.20344/amp.6521 ◽

2015 ◽

Vol 28 (5) ◽

pp. 663

Author(s):

Pedro Marques ◽

Karim Chikh ◽

Anne Charrié ◽

Rosa Pina ◽

Maria João Bugalho ◽

...

Keyword(s):

Hormone Receptor ◽

Chinese Hamster Ovary Cells ◽

Chinese Hamster ◽

Thyroid Stimulating Hormone ◽

Human Thyroid ◽

In Vitro Tests ◽

Lymphocytic Thyroiditis ◽

Blocking Activity ◽

Stimulating Hormone

Thyroid-stimulating hormone-receptor autoantibodies normally causes hyperthyroidism. However, they might have blocking activity causing hypothyroidism. A 11-year-old girl followed due to type 1 diabetes mellitus, celiac disease and euthyroid lymphocytic thyroiditis at diagnosis. Two years after the initial evaluation, thyroid-stimulating hormone was suppressed with normal free T4; nine months later, a biochemical evolution to hypothyroidism with thyroid-stimulating hormone-receptor autoantibodies elevation was seen; the patient remained always asymptomatic. Chinese hamster ovary cells were transfected with the recombinant human thyroid-stimulating hormone -receptor, and then exposed to the patient´s serum; it was estimated a ‘moderate’ blocking activity of these thyroid-stimulating hormone-receptor autoantibodies, and concomitantly excluded stimulating action. In this case, the acknowledgment of the blocking activity of the serum thyroid-stimulating hormone-receptor autoantibodies, supported the hypothesis of a multifactorial aetiology of the hypothyroidism, which in the absence of the in vitro tests, we would consider only as a consequence of the destructive process associated to lymphocytic thyroiditis.

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