Serum BAFF Concentrations in Patients with Graves' Disease and Orbitopathy before and after Immunosuppressive Therapy

Endocrine Unit, Department of Medical Sciences, University of Milan and Fondazione Cà Granda Istituto di Ricovero e Cura a Carattere Scientifico, 20122 Milan, Italy.
The Journal of Clinical Endocrinology and Metabolism (Impact Factor: 6.21). 03/2012; 97(5):E755-9. DOI: 10.1210/jc.2011-2614
Source: PubMed


B cells are known to play a key role in the pathogenesis of autoimmune disease. B lymphocyte activating factor (BAFF), a member of TNF family, promotes autoantibody production by increasing B cell survival and proliferation. Serum BAFF concentrations have been found to be increased in systemic lupus erythematosus, rheumatoid arthritis, and Sjogren's syndrome.
We have measured serum BAFF concentrations in patients with Graves' disease (GD) with or without Graves' orbitopathy (GO) and in active GO in relation to immunosuppressive treatment.
Forty-two patients and nine normal controls were studied. Thirty-four patients had GO, which was active in 23. Of these, nine were treated with rituximab (RTX) and 14 with i.v. methylprednisolone (MP). Serum BAFF concentrations were measured at baseline in all patients, at peripheral B cell depletion and repopulation after RTX, and after therapy with MP.
Serum basal BAFF concentrations in GD patients were significantly higher when compared with normal controls (P = 0.0001), and no difference was observed in those with active or inactive GO. Serum BAFF concentrations were also significantly correlated with serum antithyroglobulin antibodies (P = 0.04) but not with sex, age, smoking habits, therapy for thyroid disease, and serum antithyroperoxidase antibodies and TSH receptor antibodies. After RTX, there was an increase of serum BAFF concentrations at the time of B cell depletion (P = 0.02) but also at B cell repopulation (P = 0.04). In patients treated with MP, serum BAFF concentrations decreased significantly after therapy (P < 0.01).
We report that serum BAFF concentrations are elevated in patients with GD, in whom hyperthyroidism is known to be based on a B-cell-driven pathophysiological mechanism. In active GO, BAFF further increases after therapy with RTX as a consequence of the B cell depletion per se. The decrease of serum BAFF after iv steroids suggests that MP may exert an immunosuppressive effect by modifying B-cell-derived immune reactions.

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    • "Serum BAFF concentrations have been noted to be increased in autoimmune disease [39] Animal studies with BAFF and APRIL inhibitors have shown a reduction in hyperthyroxinemia and TSH receptor antibodies in a murine model of Grave's disease [40]. In humans with Grave's disease, the BAFF levels significantly correlated with Tg-Ab but not with TPO-Ab nor TSHR-Ab [41]. "
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    ABSTRACT: Autoantibodies to thyroglobulin and thyroid peroxidase are common in the euthyroid population and are considered secondary responses and indicative of thyroid inflammation. By contrast, autoantibodies to the TSH receptor are unique to patients with Graves' disease and to some patients with Hashimoto's thyroiditis. Both types of thyroid antibodies are useful clinical markers of autoimmune thyroid disease and are profoundly influenced by the immune suppression of pregnancy and the resulting loss of such suppression in the postpartum period. Here, we review these three types of thyroid antibodies and their antigens and how they relate to pregnancy itself, obstetric and neonatal outcomes, and the postpartum.
    Journal of Thyroid Research 04/2013; 2013(1):182472. DOI:10.1155/2013/182472
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    ABSTRACT: Aim: The aim of our study was to highlight the palpebral and ocular signs in patients with thyroid dysfunction. These patients are sometimes poorly evaluated in routine check ups. This information is useful both to the practicing ophthalmologist but also to the specialist in endocrinology. Patients and methods: 100 patients were enrolled. The patients had been diagnosed with the Basedow-Graves-Flajani syndrome or had hypothyroidism or thyroidits. Orbital, adnexal and ocular signs were recorded in all patients. Results: Seventeen oculopalpebral signs were observed in a total of 100 patients (73 females and 27 males). These were as follows: Dalrymple, Von Graefe, Rosenbach, Inglese, Gifford, Enroth, Jellinek, Stellwag, Jeffroy, Topolansky, Moebius, Suker, Sattler, Sainton, Ballet, Cowens, Exphothalmos. Discussion: The specialist in endocrinology has many laboratory and clinical tools in the diagnosis of patients with thyroid dysfunction. However, with a better awareness of the oculopalpebral signs both the ophthalmologist and the endocrinologist can work together in a multidisciplinary team towards the management of these patients.
    La Clinica terapeutica 11/2012; 163(6):e397-e400. · 0.33 Impact Factor
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    ABSTRACT: B cell-activating factor (BAFF) is important in the development and maturation of B cells and their progeny-plasma blasts and plasma cells. There is increasing evidence that BAFF is involved in the pathogenesis of several autoimmune diseases including myasthenia gravis. Increased expression of BAFF and receptors for BAFF have been demonstrated in thymus of patients with myasthenia gravis, and an increase in serum levels of BAFF have been reported in patients with myasthenia gravis. While the exact role of BAFF in the pathogenesis of myasthenia gravis is not clear, BAFF and its receptors may provide potential targets for therapy in patients with myasthenia gravis.
    Annals of the New York Academy of Sciences 12/2012; 1274(1):60-7. DOI:10.1111/j.1749-6632.2012.06842.x · 4.38 Impact Factor
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