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Complement component C9 in Graves' disease
D A Oleesky1, S Ratanachaiyavong, M Ludgate
1Department of Medical Biochemistry, University Hospital of Wales, UK.
Insights
Elevated levels of complement component 9 (C9) were found in Graves' disease patients, suggesting its involvement in the condition. C9 levels decreased with antithyroid drug treatment, further supporting its role in Graves' disease pathogenesis.
Area of Science:
- Immunology
- Endocrinology
Background:
- Complement component 9 (C9) is crucial for membrane attack complex formation and acts as an acute phase protein.
- The role of C9 in Graves' disease, an autoimmune thyroid disorder, remains unclear.
Purpose of the Study:
- To investigate the potential involvement of C9 in the pathogenesis of Graves' disease.
- To measure plasma C9 concentrations in patients with hyperthyroid Graves' disease and compare them to normal subjects.
Main Methods:
- Plasma C9 concentrations were measured using an automated two-site immunoradiometric assay with monoclonal antibodies.
- Immunohistochemical staining and radiolabelled antibody binding were used to assess C9 localization in thyroid tissue.
Main Results:
- Plasma C9 concentrations were significantly higher in hyperthyroid Graves' disease patients compared to normal individuals.
- C9 levels decreased significantly after treatment with antithyroid drugs but not after radioactive iodine therapy.
- Monoclonal antibodies to C9 bound to thyroid follicular basement membranes in Graves' disease tissue, but not in normal tissue.
Conclusions:
- C9, and by extension the membrane attack complex, may play a role in the pathogenesis of Graves' disease.
- The findings suggest C9 as a potential biomarker or therapeutic target in Graves' disease management.
Abstract:
C9, the terminal component of complement, is the key part of the membrane attack complex formed as a result of complement activation; it has also been reported to be an acute phase protein. Its potential role in Graves' disease has been studied by measuring plasma C9 concentrations using an automated two-site immunoradiometric assay employing monoclonal antibodies, whose binding to thyroid tissue has also been investigated. The plasma C9 concentration in patients with hyperthyroid Graves' disease (86.3 +/- 21.6 mg/l, mean +/- SD; n = 49) was significantly increased (P less than 0.001) compared with normal subjects (60.4 +/- 13.4 mg/l; n = 48). In contrast, the plasma concentration of C-reactive protein, a marker of the acute phase response, was not significantly different between the two groups. The plasma C9 concentration in patients with hyperthyroid Graves' disease decreased significantly (P less than 0.01) after treatment with antithyroid drugs (carbimazole or methimazole; n = 14), but not after radioactive iodine (131I) treatment (n = 18). Immunohistochemical staining demonstrated that monoclonal antibody to C9 bound to the basement membranes of thyroid follicular cells of Graves' thyroid tissue but not to normal thyroid tissue. Radiolabelled monoclonal antibody to C9 bound to membrane fragments prepared from thyroid glands from two patients with Graves' disease. We conclude that C9, and by implication the membrane attack complex, may be involved in the pathogenesis of Graves' disease.