Extraocular muscle antibodies and the occurrence of ophthalmopathy in Graves' disease.
OBJECTIVE
The aim of this study was twofold: first to investigate the presence of extraocular muscle antibodies (EMAb) in sera of Graves' patients with ophthalmopathy characterized by clinical extraocular muscle (EM) involvement; second to evaluate in Graves' patients without ophthalmopathy whether longitudinal variations of EMAb have a predictive role for the development of eye disease.


METHODS
We evaluated sera of Graves' patients previously tested for G2sAb and FpAb; in particular, sera of 32 patients with moderate or severe ophthalmopathy and EM involvement: 18 with active disease (group 1), 14 with inactive disease (group 2). Moreover, we evaluated longitudinally sera of 19 Graves' patients without ophthalmopathy previously tested for anti-GS2 (G2sAb) and antiflavoprotein antibodies (FpAb; group 3). During the 18-month follow-up, four of them did not develop ophthalmopathy (group 3a), and 15 did: seven developed eye disease (group 3b) with clinical EM involvement. In particular, moderate disease and clinical activity score (CAS) >/= 4 in four of them, severe ophthalmopathy and CAS </= 1 in three were observed. The remaining eight patients showed moderate ophthalmopathy and CAS >/= 4 without EM involvement (group 3c).


METHODS
EMAb were evaluated in all samples by indirect immunofluorescence method.


RESULTS
EMAb were detected in 13 out of 18 patients (72.2%) in group 1 (titre 1/32-1/128) and in five out of 14 patients (35.7%) in group 2 (titre 1/2-1/8). As regards to group 3, at the start of the study EMAb were detected in 13 out of 19 patients (72%) at titres 1/2-1/8; during the follow-up they became or persisted negative in all patients in group 3a, while they increased at titres ranging from 1/64 to 1/128 in all patients in group 3b before the onset of ophthalmopathy. Finally, in group 3c, four patients showed a mild increase (1/8-1/16) of EMAb before the onset of eye disease, while four patients were negative during the entire follow-up.


CONCLUSIONS
Our results indicate that EMAb are a good marker of ophthalmopathy with EM involvement and their titre is higher in patients with active than in those with inactive disease. Thus, even if our results must be confirmed on a larger cohort of patients, the increase of EMAb in patients with Graves' disease could be considered as a risk factor for the development of ophthalmopathy with subclinical/clinical EM impairment. In this connection we propose the evaluation of EMAb, in Graves' patients with subclinical and clinical ophthalmopathy, as a simple and sensitive marker of the EM inflammatory process.
de Bellis
A
A
Department of Clinical and Experimental Medicine and Surgery 'F. Magrassi and A. Lanzara', Second University of Naples, Italy. annamaria.debellis@unina2.it
Perrino
S
S
Coronella
C
C
Sansone
D
D
Ruocco
G
G
Tirelli
G
G
Di Martino
S
S
Conte
M
M
Bellastella
G
G
Wall
J R
JR
Bellastella
A
A
Bizzarro
A
A
D000208:Acute Disease; D000328:Adult; D000906:Antibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D005128:Eye Diseases / Q000276:immunology*; D005260:Female; D006111:Graves Disease / Q000276:immunology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009801:Oculomotor Muscles / Q000276:immunology*; D011237:Predictive Value of Tests; D018709:Statistics, Nonparametric
D000906:Antibodies; D015415:Biomarkers