Recombinant monoclonal thyrotropin-stimulation blocking antibody (TSBAb) established from peripheral lymphocytes of a hypothyroid patient with primary myxedema
| Autor: | Naotetsu Kanamoto, Takashi Akamizu, Yuji Hataya, Yoshiyuki Hattori, Tomohiko Mori, Kenji Moriyama, Fumihiko Matsuda, Kazuwa Nakao, Misa Saijo, Jyoji Okuda |
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| Rok vydání: | 2004 |
| Předmět: |
endocrine system
endocrine system diseases medicine.drug_class Endocrinology Diabetes and Metabolism Molecular Sequence Data Thyrotropin Monoclonal antibody law.invention Mice Endocrinology Hypothyroidism law Cricetinae Blocking antibody Myxedema medicine Animals Humans Lymphocytes B cell Mice Inbred BALB C biology Base Sequence Antibodies Monoclonal Sequence Analysis DNA medicine.disease Molecular biology Graves Disease Recombinant Proteins medicine.anatomical_structure Monoclonal biology.protein Recombinant DNA Immunoglobulin Light Chains Antibody Clone (B-cell biology) Immunoglobulin Heavy Chains Immunoglobulins Thyroid-Stimulating |
| Zdroj: | Journal of endocrinological investigation. 26(11) |
| ISSN: | 0391-4097 |
| Popis: | Anti-TSH receptor antibodies (TRAbs) have been known to be involved in Graves’ disease and primary hypothyroidism. We previously isolated and reconstituted immunoglobulin (Ig) genes of Epstein-Barr virus-transformed B cell clones producing monoclonal TRAbs obtained from Graves’ patients. In the present study, we performed a similar experiment using a B cell clone, 32A-5, derived from a patient with primary hypothyroidism. The variable region genes of Ig heavy (H) and light (L) chains were isolated and sequenced from the 32A-5 clone. A significant number of somatic mutations were found in variable regions of H and L chain gene segments. Each pair of H and L chain cDNAs was ligated into an expression vector for IgG1 production and stably introduced into myeloma cells. The transfectants were injected ip into BALB/c mice to yield ample volume of the antibody for following applications. Interactions of recombinant 32A-5 with Graves’ sera with varying thyroid-stimulating antibody (TSAb) activities were studied. The recombinant antibody tended to suppress TSAb activities in 10 of 15 Graves’ sera, in which four were significantly inhibited. In summary, this is the first study to analyze human monoclonal TSH-stimulation blocking antibodies (TSBAb) at the molecular level. Use of human recombinant monoclonal TSBAb may be an analytical tool for molecular-basis etiology and an alternative therapeutic path for Graves’ disease. |
| Databáze: | OpenAIRE |
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