Autoantibodies to the flavoprotein subunit of succinate dehydrogenase: analysis of specificity in autoimmune thyroid disease

OBJECTIVE Thyroid-associated ophthalmopathy is a progressive eye disorder a ffecting the extraocular muscle and orbital connective tissue and is consid ered to have an autoimmune aetiology. A recent study reported a close relat ionship between serum antibodies against the flavoprotein subunit of succin ate dehyhdrogenase (SDHFp) and active thyroid-associated ophthalmopathy inv olving eye muscle damage. The aim of the present study was to develop a sen sitive and quantitative radiobinding assay for the detection of antibodies to the flavoprotein subunit of succinate dehydrogenase and to use this to d etermine the distribution of antibodies in different patient groups. DESIGN AND PATIENTS Serum samples from the following patient groups were an alysed: 20 systemic lupus erythematosus; 20 Addison's disease; 26 autoimmun e hypothyroidism; 28 Graves' hyperthyroidism; 12 pretibial myxoedema; 25 th yroid-associated ophthalmopathy. Sera from 20 healthy subjects were used as controls. [S-35]-labelled succinate dehydrogenase flavoprotein was produce d in an in vitro transcription-translation system and subsequently used in immunoprecipitation experiments with sera from patient and control groups t o test for the presence of antibodies to the flavoprotein. RESULTS Succinate dehydrogenase flavoprotein antibodies were detected in fi ve of the 20 (25%) patients with Addison's disease, six of the 20 (30%) wit h systemic lupus erythematosus, five of the 26 (19%) with autoimmune hypoth yroidsm, six of the 28 (21%) with Graves' hyperthyroidism, two of the 12 (1 7%) with pretibial myxoedema and three of the 25 (12%) with thyroid-associa ted ophthalmopathy. The frequencies of flavoprotein antibodies were signifi cantly greater than controls (P-value < 0.05) for patients with systemic lu pus erythematosus (P = 0.02), but not for patients with either Addison's di sease (P = 0.05), pretibial myxoedema (P = 0.13), Graves' hyperthyroidism ( P = 0.07), autoimmune hypothyroidism (P = 0.06) or thyroid-associated ophth almopathy (P = 0.24). For the patients with thyroid-associated ophthalmopat hy, the frequency of SDHFp antibodies did not appear to be related to the l ength of time from diagnosis: the group containing samples taken less than one year from diagnosis showed no increased frequency of SDHFp antibodies w hen compared to controls (P = 0.10), with three of the 78 (17%) patients be ing positive. With respect to seven patients with thyroid-associated ophtha lmopathy diagnosed for more than a year, SDHFp antibodies were not detected in any of their serum samples. In addition, the clinical severity of the d isease, as recorded by the NOSPECS classification, did not correlate with t he frequency of SDHFp antibodies: P = 0.13, 0.33 and 0.38, respectively, fo r patients with Grade II, III and IV ophthalmopathy. Similar results were a lso found in the case of patients with pretibial myxoedema and eye disease: P = 0.06 for patients with Grade III ophthalmopathy and, SDHFp antibodies were not detected in any of the sera taken from patients with Grade IV opht halmopathy. In addition, no association was found between disease duration and the frequency of antibodies to the flavoprotein in this patient group. CONCLUSIONS Our results indicate that succinate dehydrogenase flavoprotein antibodies are not a suitable marker for thyroid-associated ophthalmopathy, at least with the assay system used, as they can be found in patients who do not have eye disease and therefore lack the disease specificity required of a diagnostic tool.