Characterization of thyroglobulin epitopes in Sardinian adults and juveniles with Hashimoto's thyroiditis: evidence against a major effect of age and genetic background on B-cell epitopes.
BACKGROUND
Using recombinant human monoclonal thyroglobulin antibodies expressed as Fab molecules (TgAb-Fab), we have recently confirmed the restriction of Tg epitopes in Hashimoto's thyroiditis (HT).


OBJECTIVE
To investigate Tg epitopes of serum TgAb in HT adults and HT juveniles from a geographically isolated area (Sardinia).


METHODS
Serum TgAb of 39 Sardinian HT adults, 53 Sardinian HT juveniles and 45 non-Sardinian HT adults were evaluated. The binding of serum TgAb to Tg in ELISA was inhibited by four recombinant human TgAb-Fab, identifying Tg epitopic regions A-D. The percentage of Tg binding inhibition was calculated comparing the binding of serum TgAb in presence of each TgAb-Fab with that in its absence.


RESULTS
In the whole cohort of 137 patients, A region TgAb-Fab induced the highest levels of inhibition (55.3 +/- 17.8%) (mean +/- SD). Lower levels of inhibition were induced by TgAb-Fab of regions B (27.8 +/- 25.8%), C (26.8 +/- 24.6%) and D (17.5 +/- 18.4%). In Sardinian HT adults inhibition by TgAb-Fab of regions A, B and C were comparable to Sardinian HT juveniles; the marginal D region TgAb-Fab induced a slightly higher inhibition (22.1 vs. 13.8%; P = 0.034) in the former than in the latter group. In Sardinian and non-Sardinian HT adults inhibitions by the four TgAb-Fab were similar.


CONCLUSIONS
In HT, the Tg epitope pattern of serum TgAb was similar in juveniles and adults from a geographically restricted area and in two adult populations from different geographical areas. Thus, in HT, neither age nor genetic background appear to influence B-cell epitopes.
Latrofa
Francesco
F
Department of Endocrinology, WHO Collaborating Centre for the Diagnosis and Treatment of Thyroid Cancer and Other Thyroid Diseases, University of Pisa, Via Cisanello 2, Pisa, Italy. latrofaf@libero.it
Ricci
Debora
D
Vitti
Paolo
P
Prinzis
Alessia
A
Cambuli
Valentina Maria
VM
Ghiani
Mariangela
M
Pilia
Sabrina
S
Carta
Daniela
D
Loche
Sandro
S
Pinchera
Aldo
A
Mariotti
Stefano
S
D000293:Adolescent; D000328:Adult; D000937:Antigen-Antibody Reactions / Q000187:drug effects; D001324:Autoantigens / Q000276:immunology; D002648:Child; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D005006:Ethnicity / Q000235:genetics; D005260:Female; D050031:Hashimoto Disease / Q000276:immunology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D007453:Iodide Peroxidase / Q000276:immunology; D033862:Iron-Binding Proteins / Q000276:immunology; D007558:Italy; D008297:Male; D013954:Thyroglobulin / Q000276:immunology*; D044465:White People / Q000235:genetics
D001324:Autoantigens; D018985:Epitopes, B-Lymphocyte; D007140:Immunoglobulin Fab Fragments; D033862:Iron-Binding Proteins; D013954:Thyroglobulin; C056658:TPO protein, human; D007453:Iodide Peroxidase