Serum BAFF Concentrations in Patients with Graves' Disease and Orbitopathy before and after Immunosuppressive Therapy
ABSTRACT 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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ABSTRACT: Systemic autoimmune diseases can damage nearly every tissue or cell type of the body. Although a great deal of progress has been made in understanding the pathogenesis of autoimmune diseases, current therapies have not been improved, remain unspecific and are associated with significant side effects. Because dendritic cells (DCs) play a major role in promoting immune tolerance against self-antigens (self-Ags), current efforts are focusing at generating new therapies based on the transfer of tolerogenic DCs (tolDCs) during autoimmunity. However, the feasibility of this approach during systemic autoimmunity has yet to be evaluated. TolDCs may ameliorate autoimmunity mainly by restoring T cell tolerance and, thus, indirectly modulating autoantibody development. In vitro induction of tolDCs loaded with immunodominant self-Ags and subsequent cell transfer to patients would be a specific new therapy that will avoid systemic immunosuppression. Herein, we review recent approaches evaluating the potential of tolDCs for the treatment of systemic autoimmune disorders.International Journal of Molecular Sciences 09/2014; 15(9):16381-16417. DOI:10.3390/ijms150916381 · 2.34 Impact Factor
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ABSTRACT: Graves' orbitopathy (GO) is the main extrathyroidal manifestation of Graves disease and a rare disease in its severe expressions. Moderate-to-severe GO represents a therapeutic challenge. Established nonsurgical treatments include glucocorticoids (most commonly given intravenously), cyclosporine, and orbital radiotherapy. However, results are not always satisfactory, and a relevant proportion of GO patients need some kind of rehabilitative surgery (orbital decompression, squint surgery, eyelid surgery) once GO is inactivated. Biological agents have been used in several autoimmune disorders, with contrasting results. Current better understanding of the pathogenesis of GO allows us to identify pathways that might be the target of biologics. T and B cells, cytokines, and peroxisome proliferator-activated receptor-γ might all be targeted by treatments. It is extremely difficult to design and perform sufficiently powered randomized controlled studies that may support the role of targeted therapies. For the time being, rituximab, a monoclonal antibody depleting CD20-positive B cells, appears the most promising agent, but so far its use relies on the results of small and uncontrolled studies.Ophthalmic Plastic and Reconstructive Surgery 07/2014; 30(5). DOI:10.1097/IOP.0000000000000221 · 0.91 Impact Factor
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ABSTRACT: Graves' disease (GD) is an autoimmune disease that involves aberrant B- and T-lymphocyte responses. Detailed knowledge about lymphocyte subpopulation composition will therefore enhance our understanding of the pathogenesis of GD and might support the development of new immunomodulatory treatment approaches. To gain detailed insight into the composition of the peripheral blood lymphocyte compartment in GD before and during anti-thyroid drug therapy. Major B- and T-lymphocyte subpopulations were investigated by flow cytometry in peripheral blood from newly diagnosed GD patients (n=5), GD patients treated with anti-thyroid drugs (n=4), patients with recurrent GD (n=7) and healthy controls (HC; n=10). in GD patients numbers of activated T lymphocytes (HLA-DR(+) and CD25(+) ) were increased. The B-lymphocyte compartment in GD was characterized by significantly higher numbers of transitional (CD38(high) CD27(-) , p<0.03) and pre-naive mature (CD38(low) CD27(-) IgD(+) CD5(+) , p<0.04) B lymphocytes, while memory populations were slightly decreased. The increased numbers of CD5(+) , transitional and pre-naive mature B lymphocytes correlated positively with fT4 plasma levels. GD is associated with increased numbers of activated T lymphocytes and transitional and pre-naive mature CD5(+) B lymphocytes within the peripheral blood. The increase in CD5(+) B-lymphocytes was mainly due to an increase in transitional and pre-naive mature B lymphocytes. Increased fT4 plasma levels might be associated with this increase in transitional and pre-naive mature CD5(+) B lymphocytes.Clinical & Experimental Immunology 07/2013; DOI:10.1111/cei.12183 · 3.28 Impact Factor