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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2004-3-10
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0391-4097
pubmed:author
pubmed:issnType
Print
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1076-80
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15008244-Animals, pubmed-meshheading:15008244-Antibodies, Monoclonal, pubmed-meshheading:15008244-Base Sequence, pubmed-meshheading:15008244-Cricetinae, pubmed-meshheading:15008244-Graves Disease, pubmed-meshheading:15008244-Humans, pubmed-meshheading:15008244-Hypothyroidism, pubmed-meshheading:15008244-Immunoglobulin Heavy Chains, pubmed-meshheading:15008244-Immunoglobulin Light Chains, pubmed-meshheading:15008244-Immunoglobulins, Thyroid-Stimulating, pubmed-meshheading:15008244-Lymphocytes, pubmed-meshheading:15008244-Mice, pubmed-meshheading:15008244-Mice, Inbred BALB C, pubmed-meshheading:15008244-Molecular Sequence Data, pubmed-meshheading:15008244-Myxedema, pubmed-meshheading:15008244-Recombinant Proteins, pubmed-meshheading:15008244-Sequence Analysis, DNA, pubmed-meshheading:15008244-Thyrotropin
pubmed:year
2003
pubmed:articleTitle
Recombinant monoclonal thyrotropin-stimulation blocking antibody (TSBAb) established from peripheral lymphocytes of a hypothyroid patient with primary myxedema.
pubmed:affiliation
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't