Human monoclonal thyroglobulin autoantibodies: epitopes and immunoglobulin genes.
TLDR
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.Abstract:
Autoantibodies to thyroglobulin (TgAbs) are common markers of thyroid autoimmunity, but relatively few human monoclonal TgAbs have been described. From a panel of 64 human monoclonal TgAbs (isolated from a thyroid-disease derived combinatorial Ig gene library), we selected seven with unique genetic features for detailed characterization. These TgAbs preferentially recognize native (not denatured) Tg, like serum autoantibodies. Most have high affinities for Tg (dissociation constant 10(-10) to 10(-9) m). Their light (L) chain Ig genes are not unusual, but four of the five heavy (H) chain genes are new. Moreover, one H chain belongs to the small VH2 family, not previously reported for autoantibodies to Tg or thyroid peroxidase. The TgAbs inhibit the binding to Tg of the thyroid donor's serum autoantibodies, indicating epitopic overlap. Competition analysis (surface plasmon resonance) shows that the TgAbs recognize overlapping epitopes in an immunodominant region on the Tg dimer ( approximately 660 kDa). Two major and several minor epitopic regions were defined, each associated with a particular H + L chain combination. In conclusion, our 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.read more
Citations
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CD32b expression is down-regulated on double-negative memory B cells in patients with Hashimoto's thyroiditis.
Yalei Liu,Yan Gong,Chenxue Qu,Yang Zhang,Ran You,Nan Yu,Guizhi Lu,Youyuan Huang,Hong Zhang,Ying Gao,Yanming Gao,Xiaohui Guo +11 more
TL;DR: The results suggest that abnormal B cell subset distribution and decreased CD32b expression on DN memory cells might be involved in the pathogenesis of HT.
Journal ArticleDOI
Thyroglobulin autoantibodies switch to immunoglobulin (Ig)G1 and IgG3 subclasses and preserve their restricted epitope pattern after 131I treatment for Graves' hyperthyroidism: the activity of autoimmune disease influences subclass distribution but not epitope pattern of autoantibodies
Francesco Latrofa,Debora Ricci,Lucia Montanelli,Paolo Piaggi,Barbara Mazzi,Francesca Bianchi,Federica Brozzi,P Santini,Emilio Fiore,Michele Marinò,Massimo Tonacchera,Paolo Vitti +11 more
TL;DR: It is concluded that 131I treatment for GD increases the levels of the complement‐activating IgG1 and IgG3 subclasses and does not influence significantly the epitope pattern of TgAb.
Journal ArticleDOI
Characterization of a new highly sensitive immunometric assay for thyroglobulin with reduced interference from autoantibodies.
Marianne Nordlund Broughton,Ragnhild V. Nome,Ingvill Sandven,Elisabeth Paus,Trine Bjøro,Trine Bjøro +5 more
TL;DR: A panel of monoclonal antibodies selected to bind Tg in the presence of Tg autoantibodies is produced and a sensitive immunoassay for Tg is developed with minor interference by hTgAbs with good agreement between the new high sensitive immunofluorometric assay (IFMA) and two well-established Tg assays from Brahms Kryptor and Roche Diagnostics.
Patent
Immunoassay for detecting thyroglobulin utilizing soybean produced recombinant thyroglobulin
TL;DR: In this article, a soybean derived human thyroglobulin, methods of producing human thyroidoglobulin in plants such as soybean, and novel diagnostic applications for the detection and stratification of endocrine malignancies including thyroid cancer and thyroiditis are presented.
References
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The repertoire of human germline VH sequences reveals about fifty groups of VH segments with different hypervariable loops.
TL;DR: The polymerase chain reaction and VH family-based primers are used to clone and sequence 74 human germline VH segments from a single individual and a directory is built to include all known germline sequences.
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Serum thyroglobulin autoantibodies: prevalence, influence on serum thyroglobulin measurement, and prognostic significance in patients with differentiated thyroid carcinoma.
Carole A. Spencer,M Takeuchi,M. Kazarosyan,C. C. Wang,Richard B. Guttler,Peter Singer,Shireen Fatemi,Jonathan S. LoPresti,John T. Nicoloff +8 more
TL;DR: The RIA method used in this study provided more clinically appropriate serum Tg values in the group of TgAb-positive patients with metastatic DTC and may be an additional clinically useful tumor marker parameter for following T gAb- positive patients.
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Content and organization of the human Ig VH locus: definition of three new VH families and linkage to the Ig CH locus.
Jeffrey E. Berman,S. J. Mellis,Roberta R. Pollock,Cassandra L. Smith,Heikyung Suh,B. Heinke,C. Kowal,Urvashi Surti,Leonard Chess,C. R. Cantor +9 more
TL;DR: The first report of the physical linkage of the variable and constant loci of a human Ig gene family is provided by demonstrating that the most proximal known human VH segments lie within 100 kb of the constant region locus.
Journal ArticleDOI
A directory of human germ-line Vχ segments reveals a strong bias in their usage
TL;DR: Comparison with 236 rearranged sequences revealed that no more than 24 of these germ‐line sequences could be assigned rearranged counterparts, that some of these were rarely used, and that only about 11 sequences are used frequently, suggesting that the expressed Vχ repertoire is mainly derived from a limited number of segments.
Journal ArticleDOI
Disappearance of humoral thyroid autoimmunity after complete removal of thyroid antigens.
Luca Chiovato,Francesco Latrofa,Lewis E. Braverman,Furio Pacini,Marco Capezzone,Lucio Masserini,Lucia Grasso,Aldo Pinchera +7 more
TL;DR: A large group of patients with differentiated thyroid carcinoma who had serum thyroid peroxidase, thyroglobulin, or TSH-receptor antibodies due to coexistent thyroid autoimmune disease were studied, finding gradual disappearance of antibodies gradually disappeared in most patients.