The Spectrum and Significance of Autoantibodies Reacting with the Thyrotropin Receptor

Zakarija, M.; Jm, McKenzie

doi:10.1016/s0889-8529(18)30483-3

Cited by 76 publications

(28 citation statements)

References 81 publications

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“…Hyperthyroidism in Graves' disease (GD) is based on a B-cell driven mechanism leading to sustained production of immunoglobulins G stimulating the thyroid stimulating hormone (TSH) receptor on the thyrocytes (1,2). This phenomenon emerges in the context of an autoimmune thyroiditis characterized by typical lymphocytic infiltration of the thyroid tissue (3).…”

Section: Introductionmentioning

confidence: 99%

Treatment of Graves’ disease and associated ophthalmopathy with the anti-CD20 monoclonal antibody rituximab: an open study

Salvi¹,

Vannucchi²,

Campi³

et al. 2007

eur j endocrinol

237

187

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Introduction: Hyperthyroid Graves' disease (GD) is a B-cell-mediated condition caused by TSH receptor antibodies (TRAb), which decline when GD remits. Anti-CD20 monoclonal antibody rituximab (RTX) induces transient B-cell depletion that may potentially modify the active inflammatory phase of thyroid-associated ophthalmopathy (TAO). Methods: Nine patients with GD, (seven with active TAO, two with mild lid signs) were studied. The trial was only approved as an open pilot study; thus we compared the effect of RTX therapy to that of i.v. glucocorticoids (IVGC) in 20 consecutive patients. Patients were treated with RTX (1000 mg i.v. twice at 2-week interval) or with IVGC (500 mg i.v. for 16 weeks). TAO was assessed by the clinical activity score (CAS) and severity was classified using NOSPECS (No signs or symptoms; Only signs (lid); Soft tissue involvement; Proptosis, Extraocular muscle involvement; Corneal involvement; Sight loss). Thyroid function and lymphocyte count were measured by standardized methods. Results: All patients attained peripheral B-cell depletion with the first RTX infusion. Minor side effects were reported in three patients. Thyroid function was not affected by RTX therapy and hyperthyroid patients required therapy with methimazole. After RTX, the changes in the levels of thyroglobulin antibodies, thyroperoxidase antibodies and TRAb were neither significant nor correlated with CD20C depletion (PZNS). CAS values before RTX were 4.7G0.5 and decreased to 1.8G0.8 at the end of follow-up (P!0.0001) and more significantly compared with IVGC (P!0.05). Proptosis decreased significantly after RTX both in patients with active TAO (ANOVA; P!0.0001) and those with lid signs (ANOVA; P!0.003). The degree of inflammation (class 2) decreased significantly in response to RTX (ANOVA; P!0.001). Relapse of active TAO was not observed in patients treated with RTX, but occurred in 10% of those treated with IVGC, who also experienced adverse effects more frequently (45 vs 33% of patients). Conclusions: RTX positively affects the clinical course of TAO, independently of either thyroid function or circulating antithyroid antibodies, including TRAb. If our findings are confirmed in large controlled studies, RTX may represent a useful therapeutic tool in patients with active TAO.

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Section: Introductionmentioning

confidence: 99%

Treatment of Graves’ disease and associated ophthalmopathy with the anti-CD20 monoclonal antibody rituximab: an open study

Salvi¹,

Vannucchi²,

Campi³

et al. 2007

eur j endocrinol

237

187

View full text Add to dashboard Cite

show abstract

“…Hyperthyroidism in Graves' disease (GD) is an autoimmune disease caused by immunoglobulins G stimulation of the thyroid stimulating hormone (TSH) receptor on the thyrocytes [1,2]. It arises as a consequence of an autoimmune thyroiditis with typical lymphocytic infiltration of the thyroid tissue [3].…”

Section: Introductionmentioning

confidence: 99%

Rituximab Induces Distinct Intraorbital and Intrathyroidal Effects in One Patient Satisfactorily Treated for Graves’ Ophthalmopathy

Bonara

Vannucchi

Campi

et al. 2007

Clinic Rev Allerg Immunol

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Hyperthyroid Graves' disease (GD) is a B-cell-mediated disease caused by antibodies stimulating the thyroid stimulating hormone (TSH) receptor (TRAb). A proportion of patients (40-60%) present with an associated ophthalmopathy (TAO), a progressive inflammatory autoimmune disease of the retroorbital tissue. We thought that the anti-CD20 monoclonal antibody rituximab (RTX), by inducing transient B-cell depletion, may potentially modify the active inflammatory phase of TAO. One patient with GD and TAO in its active phase and unresponsive to steroid, was treated with RTX. Whereas the ophthalmopathy responded to RTX therapy and a decrease in the clinical activity score from 5 to 2 was observed during the B-cell depletion, serum antithyroid antibodies, and in particular serum TRAb, were not affected by therapy. When the patient underwent total thyroidectomy, we found B-cells in the thyroid tissue specimens. The eye disease remained stable (clinical activity score=2) and the patient subsequently underwent orbital decompression to correct proptosis of the eye. At that time we did not find lymphocytes in any of the orbital tissue specimens. We believe that RTX therapy in GD may cause amelioration of ophthalmopathy by depleting total lymphocyte population in the orbit, but not lymphocyte depletion in thyroid tissue with consequent unchanged serum TRAb levels.

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“…Probably a major reason for this finding is the recognition (as reported previously in a different context [16]) that many (8 of 18 tested) of the patients had a mixture of both inhibitory and stimulating antibodies in the serum. A role for antibody that reduces biological effects of TSAb is a factor that should be in troduced into any discussion of correlation of the concen tration of TSAb and thyroid size or function.…”

Section: Discussionmentioning

confidence: 52%

“…Combinations of these two types of TSH-receptor-directed antibodies occur in individual pa tients [9,16]. By assaying IgG at several concentrations, a biphasic pattern of response, indicative of the presence of both TSAb and TBIAb, may be identified [16]; such a pat tern was observed with 8 of the 18 samples tested for TSAb. Scrum IgG was negative for TSAb in only one of the 18 but it gave a strongly positive result in the TBI assay.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Biological Significance of Leukocyte Infiltration of the Thyroid in Graves’ Disease

Levis¹,

Ghandur‐Mnaymneh

Jm³

et al. 1992

Int Arch Allergy Immunol

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Graves’ goiter size and gland function may be affected by interferon-γ influencing actions of the thyroid-stimulating antibody. Goiter weight (n = 20), lymphocytic infiltration and class II antigen expression were assessed. The largest goiters, strikingly, has least infiltration but, overall, the looked-for negative correlation between goiter size and lymphocyte infiltration did not materialize. This was presumably due, in part, to inhibiting antibodies in many (8/18) patients’ sera. In addition, our data do not support a major pathogenetic role for class II antigen in Graves’ disease.

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The Spectrum and Significance of Autoantibodies Reacting with the Thyrotropin Receptor

Cited by 76 publications

References 81 publications

Treatment of Graves’ disease and associated ophthalmopathy with the anti-CD20 monoclonal antibody rituximab: an open study

Treatment of Graves’ disease and associated ophthalmopathy with the anti-CD20 monoclonal antibody rituximab: an open study

Rituximab Induces Distinct Intraorbital and Intrathyroidal Effects in One Patient Satisfactorily Treated for Graves’ Ophthalmopathy

Evaluation of the Biological Significance of Leukocyte Infiltration of the Thyroid in Graves’ Disease

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