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R Volpé

Publications and source records attributed to R Volpé.

170 records · Page 10Linked to original sources
PubMedDate not supplied

The pathogenesis of Graves' disease.

We have hypothesized over many years that Graves' disease (GD) and the other autoimmune thyroid diseases (AITD) are each due to antigen-specific defects in suppressor (regulatory) T lymphocyte function. There have been several reports dealing with the role of regulatory T lymphocyte subsets, ie., that will prevent autoimmune disease in these and other organ-specific autoimmune diseases. In AITD, suppressor T cells have been shown to be less well activated by relevant antigen, but are normally activated by irrelevant antigen; suppressor T cells from normal persons react equally well to both. In GD, these cells have been shown to be inadequately activated by TSH receptor antigen, but are normally activated by irrelevant autoantigen. This reduction is partial only, and insufficient itself to precipitate the autoimmune disease; further insults from the environment are necessary to further reduce generalized regulatory cell activity, adding to the genetically induced specific regulatory cell dysfunction, which appears in turn to be due to a specific defect in the presentation of a specific antigen. This, in turn, may relate to abnormalities of the genes responsible for antigen presentation. The end result is activation of appropriate helper and effector T cells, the stimulation by these of appropriate B lymphocytes, and the concurrent production of cytokines. These events lead to functional changes within the target cell which itself will express Class II antigens, heat shock proteins, and intercellular adhesion molecules, all of which amplify the immune response. Moreover, the activation of helper T lymphocytes by specific antigen depends on the availability of normal amounts of antigen being presented to them by antigen-presenting cells. Thus, there is no need to invoke any primary abnormality or infection of the thyroid cell, or any cross-reacting antigen of microorganismic origin to initiate this process. What is required is an abnormality of antigen-presentation such that regulatory cells are not properly activated, plus some additive environmental disturbance acting on the immune system. GD specifically results from the production by B lymphocytes of an antibody directed against the TSH receptor which stimulates the thyrocyte in a manner similar to TSH, but for a much longer interval. There are also antibodies to the thyrotrophin (TSH) receptor which block the action of TSH. Thyroid stimulating antibody is typical of GD and is detectable in about 95% of cases, but is also seen in destructive thyroiditis transiently. It tends to decline with antithyoid drug therapy, and rises further (for several months) after 131 I treatment. It may slowly decline after subtotal thyroidectomy. It also declines in the third trimester of pregnancy but sometimes is sufficiently high to cause foetal and neonatal passive transfer GD. It tends to rebound in the mother after delivery and may result in postpartum GD. The blocking antibody may cause atrophic thyroiditis and hypothyroidism. Antimicrosomal antibody has now been shown to be antithyroperoxidase. It correlates moderately well with thyroid dysfunction in Hashimoto's thyroiditis (HT) and GD, while antithyroglobulin is of much less value. Graves' ophthalmopathy is still not well understood, and its precise relationship to Graves' hyperthyroidism has yet to be worked out. However the retroorbital fibroblast is now emerging as the most likely target cell, with retroorbital muscle involvement possibly secondary. A recent observation of a genomic point mutation on the TSH receptor on fibroblasts from patients with Graves' ophthalmopathy but not normal persons raises interesting possibilities.

Journal Article↗
PubMedDate not supplied

Effect of human thyroglobulin on the production of platelet activating factor from peripheral blood mononuclear cells from patients with autoimmune thyroid diseases.

Platelet activating factor (PAF), a phospholipid mediator, has been found to play a role in immune reactions, as well as in many pathophysiological alterations in certain disorders. To determine whether there might be a potential role of PAF in the development of autoimmune thyroid diseases (AITD) we have measured in vitro production of PAF by cultures of pokeweed mitogen-stimulated peripheral blood mononuclear cells (PBMC) obtained from 13 patients with Hashimoto's thyroiditis (HT) and 22 patients with Graves' disease (GD), as well as 18 normal control subjects. Similarly, the levels of PAF in cultures of PBMC after relevant [human thyroglobulin (Tg) and human thyroperoxidase (TPO)] antigenic stimulation in the same preparations were measured by a RIA kit. The basal values of PAF were significantly higher in the PBMC preparations from HT patients than in other two groups. In HT preparations, but not in controls, Tg antigen significantly increased the production of PAF. In GD preparations the response to Tg antigen was also present, but the release of PAF did not reach the levels in control group of preparations. Significantly lower values of PAF production were found in preparations from hyperthyroid GD when compared to the results of preparations from GD patients who were euthyroid and to the results of normal control preparations. The type of treatment and chronicity of disease may also have played some role in these findings, since those treated with radioactive iodine had lower values than those patients who became euthyroid using only antithyroid drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Lack of response of peripheral blood mononuclear cells to thyroid microsomal antigen in nontoxic nodular goiters.

The production of interferon gamma (IFN gamma) by peripheral blood mononuclear cells (PBMC) from patients with nontoxic nodular goiter (NTNG), autoimmune thyroid disease (AITD), and normal persons (NL) has been studied in vitro, with the express object of comparing NTNG and AITD. PBMC were cultured with thyroid microsomal antigen (TMc), thyroglobulin (Tg), and liver microsomal antigen (LMc) at concentrations of 0, 1, 10, 100, and 1000 ng/ml for two days. IFN gamma was measured by a spot-ELISA technique which determines the number of cells secreting IFN gamma. There were no significant differences in the basal numbers of IFN gamma secreting cells between NL, AITD, and NTNG PBMC in this study. In AITD PBMC, TMc antigen caused a significant increase in the number of IFN gamma secreting cells, compared with the numbers in unstimulated AITD PBMC (percent IFN gamma secreting cells), whereas Tg and LMc antigen caused a significant decrease in all groups. The maximal percentage change in IFN gamma secreting cells (i.e., compared to unstimulated PBMC) did not increase significantly in NTNG in response to TMc antigen, in contrast to the AITD PBMC. Based on these findings, it is concluded that NTNG PBMC are not sensitized to the thyroid antigens tested; this is unlike the findings from AITD PBMC.

Adolescent↗
PubMedDate not supplied

Comparison of measurements of in vitro production of antithyroid microsomal antibody versus antithyroid peroxidase antibody.

In vitro production of antithyroid microsomal antibody (AMA) and antithyroid peroxidase antibody (APA) by peripheral blood lymphocytes from patients with autoimmune thyroid disease (AITD) has been studied and compared, in view of the evidence for identity of the two differently measured antibodies. Peripheral non-T cells (2 x 10(5)) and autologous CD4 (helper/inducer) cells (2 x 10(5)) from patients with positive serum AMA were cultured for 7 days with pokeweed mitogen (PWM). B cells secreting AMA or APA were detected by the enzyme-linked immunosorbent assay (ELISA) spot assay. AMA or APA in the culture supernatants of these cells was also measured by ELISA. There was a significant correlation between the number of AMA- (IgG class) secreting cells and APA- (IgG class) secreting cells (r = 0.89 p less than 0.001). There was also a significant correlation between AMA- and APA-ELISA indices (r = 0.86, p less than 0.001). Furthermore, the number of AMA- or APA-secreting cells significantly correlated with AMA or APA secreted in the culture supernatants (r = 0.91, r = 0.92), respectively. These data show that peripheral blood lymphocytes from patients with AITD were able to produce antibodies against thyroid peroxidase (TPO) in vitro, as well as antibodies against thyroid microsomal antigen, after PWM stimulation. The significant correlation between in vitro AMA versus APA production, or the number of AMA- versus APA-secreting cells, accords with the evidence that TPO is identical to, or at least the major antigenic protein component of, thyroid microsomal antigen.

Adult↗
PubMedDate not supplied

[Immunological aspects of auto-immune thyroid diseases (author's transl)].

Sufficient evidence exists to relate auto-immune thyroid diseases (including both Graves-Basedow's disease and Hashimoto's thyroiditis) to primary disturbances of the lymphatic system. Currently available data underline the importance of immunological factors, either humoral or tissular, in the physiopathological expression of these diseases, their basic genetic disorder appearing to be a specific lack of "suppressor" T lymphocytes. This results in the survival and multiplication of an unwanted clone, appearing by chance, of "helper" T lymphocytes directed specifically towards the thyroid. These lymphocytes then cooperate with groups of previously existing appropriate B lymphocytes, which then produce immunoglobulins directed against the thyroid. Subtle genetic differences determine the appearance of either Graves-Basedow's disease or Hashimoto's thyroiditis with their typical clinical manifestations. In fact, these subtle genetic differences between the different groups of patients with Graves-Basedow's disease may result in the total absence of immunity control (thus preventing any immunological remission) whereas partial lack may occur with the possibility of remission. The role of stress in the development of hyperthyroidism may be related to the effects of an aggression on a T lymphocyte population already partially deficient.

Autoantibodies↗