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B S Hawe

Publications and source records attributed to B S Hawe.

8 recordsLinked to original sources
PubMed1987

An anti-idiotypic antibody against Graves' IgG.

Rabbit antibodies were raised against Graves' IgG adsorbed onto a TSH-receptor affinity and eluted thereof by [3H]NaCl. The rabbit serum absorbed against normal human IgG (ARI) still bound to Graves', control and Hashimoto's IgG preparations but in the latter two, binding was inhibited by bTSH (10 mU/ml). In addition, ARI stimulated thyroid cell cyclic AMP accumulation in both human and rat thyroid cells. The ARI preparation may, therefore, contain an "internal image" anti-idiotype causing thyroid (Ab2) stimulation, a Graves' disease specific anti-idiotype whose binding with Ab2 inhibits its ability to bind TSH and anti-anti-idiotype (Ab3) to "internal image" Ab2. In further studies, Graves' specific cross-reactive idiotype was found in 10/11 IgGs from patients with active Graves' disease. This study emphasizes the workings of Jerne's immunologic network and the complexity of polyclonal "anti-idiotypic" antibodies.

Antibodies, Anti-Idiotypic↗
PubMed1987

Polymorphism of the T cell receptor beta-chain in Graves' disease.

We investigated the T cell antigen receptor constant (TCR beta) beta-chain genes of patients with Graves' disease using restriction fragment length polymorphism analysis. Genomic DNA from patients and normal subjects was digested with the restriction endonuclease Bg1 II, transferred to nylon membranes using the Southern blot technique, and hybridized with a TCR beta probe. A significant increase in the frequency of the 10.0; 9.2-kilobase heterozygous phenotype was found in GD (68.6%) vs. 42.1% in normal subjects (P = 0.003). Using the complex phenotype TCR homozygote (hetero) DR3 as a reference (odds ratio = 1.00), we found that the risk for Graves' disease was restricted to TCR beta heterozygote/DR3+ individuals (odds ratio = 8.31; chi 2 = 11.82; P = 0.0009); in the absence of TCR beta heterozygosity, DR3 was not significantly associated with the disease. These results suggest that TCR beta chain genes also are associated with susceptibility to GD and that the association is most pronounced in (or restricted to) those individuals who are HLA DR3 positive.

Chromosomes, Human, Pair 7↗
PubMed1986

The thyroid "microsomal" antigen is an epitope on the thyrotropin receptor.

Antimicrosomal antibodies are present in the sera of most patients with autoimmune thyroiditis, and Graves' disease. It has, in general, been difficult to separate antimicrosomal activity from that directed against the thyrotropin (TSH) receptor in Graves' IgG preparations. The "microsomal" antigen has been localized to the endoplasmic reticulum and microfollicular aspect of thyrocytes; its structure is however unknown. In an attempt to identify the thyroid microsomal antigen, we studied the interaction of Hashimoto's IgG with high microsomal antibody titre and negative for thyroglobulin with purified thyroid plasma and light microsomal membranes. We allowed Hashimoto's, Graves', and control IgGs to bind to protein blots of thyroid plasma membranes resolved on SDS-PAGE under non-reducing conditions. All seven Hashimoto's IgG at a concentration of 2 mg/ml interacted with an M approximately 197,000 polypeptide corresponding to the TSH holoreceptor. By contrast to Graves' IgG (which were positive at 1 mg/ml), however, this binding was not blocked by pretreatment of the protein blots with TSH. Normal IgGs showed no binding at concentrations of up to 2 mg/ml. Both Hashimoto's and Graves' IgG interacted with TSH-affinity column-purified receptor preparations. Two of the Hashimoto's IgGs induced adenylate cyclase activation in thyroid plasma membranes, three inhibited TSH-stimulated enzyme activation, and two were without effect. Two classes of autoantibodies, other than TSH receptor directed, were encountered; one class raised to antigens common to all seven patients and another class unique to individual patients, eg, Mr 210,000 and Mr 20,000 polypeptides. We propose that the TSH receptor has multiple epitopes (functional domains), and the one to which antimicrosomal antibody bind is likely to be spatially separated from that with which Graves' IgG and TSH interact. Differences in affinity or number of sites allows for the demonstration of Graves' IgG against a background of antimicrosomal antibody.

Antigen-Antibody Reactions↗
PubMed1983

Increased frequency of HLA-DR3 and 5 in the syndromes of painless thyroiditis with transient thyrotoxicosis: evidence for an autoimmune aetiology.

We studied fifty patients with painless thyroiditis with transient thyrotoxicosis (PTTT) and a low radioiodine thyroidal uptake. In 25 PTTT occurred post-partum (P) and in the remainder was unrelated to pregnancy (U). Seventeen patients with classical subacute thyroiditis were studied for comparison. All patients were typed for HLA-A, B, C, DR antigens. Four of the P patients had recurrences with each pregnancy; two had one previous attack of U; three had a maternal history of Graves' disease; 76% of the P patients had small to moderate goitres and 76% antimicrosomal antibody titres at greater than 1:400. HLA-B35 was found in 24% of P patients compared to 17% of controls; 71% of patients with subacute thyroiditis were, by contrast, B35. Two of P were HLA-B8 positive (versus 25% of controls); 11 patients were HLA-DR3 positive and 15 (60%) HLA-DR5 positive compared to 23% and 27% of controls yielding a relative risk (RR) = 2.50 (P less than 0.05) and 3.83 (P less than 0.005), respectively. All four P patients with recurrences carried HLA-DR5. Thirteen of 25 patients in the U subgroup were HLA-DR3, yielding a RR = 3.38 (P less than 0.01); seven were HLA-DR5, with a non-significant RR = 1.12; four of U had first degree relatives with either autoimmune thyroid disorders or Type 1 diabetes mellitus. Thus, both P and U are associated with HLA-DR3, the P subgroup had in addition an increased frequency of DR5. The observed HLA associations for the PTTT syndromes favours an autoimmune rather than viral aetiology.

Autoimmune Diseases↗