ABSTRACT
BACKGROUND: It has been widely accepted that the epitope(s) and/or functional characteristics of thyrotropin receptor antibodies (TSHRAb) from Graves' patients are heterogenous among patients. However, the clinical significance of such heterogeneity has not been systematically evaluated yet. We were to elucidate and find the clinical significance of heterogeneity for TSH receptor antibodies in Graves' disease. METHODS: We measured stimulating TSHRAb (TSAb) activities using CHO-hTSHR cells, FRTL-5 cells and chimeric receptor expressing cells (Mc1 + 2 and Mc2), specific blocking TSHRAb (TSBAb) activities using Mc2 cells and TBII activities using porcine thyroid membrane in 136 patients with untreated hyperthyroid Graves' disease. RESULTS: Based on various TSHRAb activities from each patient, the patients could be categorized into 7 subgroups by cluster analysis; 1) Group 1 (n = 41) was characterized by moderate TSAb activities both in CHO-hTSHR cells and in FRTL-5 cells, typical TSAb epitope, rare blocking antibodies and high TBII activities. 2) Group 2 (n = 16) was characterized by the presence of blocking TSHRAb in most patients, albeit the other characteristics were the same as those in Group 1. 3) Group 3 (n = 19) patients had low TSAb activities both in CHO-hTSHR cells and in FRTL-5 cells, seldom had blocking TSHRAb, but they had high TBII activities. 4) Group 4 (n = 30) could be categorized as 'mild disease' group, as they had low activities in all kinds of TSHRAb assay and had low antimicrosomal antibody activities. 5) Group 5 (n = 14) was characterized by moderate TSAb activities with atypical epitope(s), rare blocking TSHRAb and moderate TBII activities. 6) Group 6 (n = 10) patients had very high TSAb activities with typical epitopes, seldom blocking TSHRAb and low TBII activities. 7) Group 7 (n = 6) was characterized by very high TSAb activities with atypical epitopes and high TBII activities. Pretreatment serum thyroid hormone level was low only in group 4 patients compared to the other 6 groups (p < 0.05). The size of goiter was significantly larger in those in group 1 and group 3 (p < 0.05) compared to the other 5 groups. The prevalence of clinically significant ophthalmopathy was higher in group 2 patients than the other 6 groups (50% vs. 27.5%, p = 0.06). Among 6 kinds of TSHRAb activities, only the blocking TSHRAb activity was significantly associated with the presence of ophthalmopathy in multivariate analysis. CONCLUSION: These results suggest that the differences in epitopes for TSAb or the presence of blocking TSHRAb is not a major factor in determining the degree of thyrotoxicosis in Graves' disease. Although the pathogenic mechanism is not clear yet, we suggest that patients with ophthalmopathy have different TSHRAb repertoire from those without ophthalmopathy in Graves' disease.
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Cluster Analysis , Comparative Study , Graves Disease/classification , Immunoglobulins, Thyroid-Stimulating/analysis , Logistic Models , Middle Aged , Multivariate Analysis , Receptors, Thyrotropin/analysis , Sensitivity and Specificity , Severity of Illness IndexABSTRACT
Uma amostra de 32 crianças e adolescentes portadoras de vitiligo localizado ou generalizado, foi avaliada para a presença de história familiar de doenças auto-imunes, disfunçäo tireóidea e presença de anticorpos antitireóideos. História familiar para tireoidopatia foi encontrada em 15,6 por cento do total da amostra e para vitiligo em 18,7 por cento. A funçäo tireóidea, avaliada através das dosagens de T3, T4 e TSH medidos por quimioluminescência, foi normal em todos os casos. Os anticorpos antitireoglobulina e antiperoxidase foram positivos em, respectivamente, 2 pacientes (6,25 por cento) e 8 pacientes (25 por cento). Concluiu-se pela alta frequência de anticorpos antitireóideos em crianças com vitiligo, o que sugere a necessidade de avaliaçäo tireóidea inicial destas crianças e posterior acompanhamento, com a finalidade de detecçäo precoce de disfunçäo tireóidea clínica ou subclínica