RESUMO
The etiology of autoimmune diseases is multifactorial with genetic factors being an important prerequisite. There are two clinical manifestations of autoimmune thyroiditis: the goitrous form (Hashimoto's thyroiditis) and the atrophic variant, which is characterized by hypothyroidism (primary myxoedema). Different genetic markers were assumed to be predisposing factors for the distinct clinical presentation. In the present study, we determined HLA A,B,C,DR,DQ alloantigens serologically and HLA-DQ by gene analysis in patients with nongoitrous autoimmune thyroiditis and randomly chosen controls. To verify the exact classifications, thyroid volume (median 5.85 ml) was measured by ultrasonography. HLA-DR5 was found in 16 of 36 (44%) patients with nongoitrous autoimmune thyroiditis and in only 26 of 175 controls (15%) (Pc = 0.0018). There was a tendency towards a lower frequency of HLA-DR7 with 6% positivity in patients vs. 29% in controls (Pc = 0.052). Regarding HLA-DQ, DQ7 was found in 17 of 35 patients (48%) vs. 21 of 98 controls (21%) (Pc = 0.028) (relative risk 3.5). No other association was found with HLA-A,B,C and HLA-DR and -DQ. Our data indicate that the genetic susceptibility to autoimmune nongoitrous thyroiditis is closely associated to HLA-DR5 and DQ7 and not distinct from goitrous disease. We conclude that factors other than genetic ones explain the different immunological and clinical manifestation of chronic lymphocytic thyroiditis.
Assuntos
Doenças Autoimunes/genética , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Mixedema/genética , Tireoidite Autoimune/genética , Doenças Autoimunes/imunologia , Suscetibilidade a Doenças/imunologia , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Antígenos HLA/genética , Antígenos HLA-DQ/sangue , Antígenos HLA-DR/sangue , Antígeno HLA-DR5/sangue , Antígeno HLA-DR5/genética , Humanos , Masculino , Mixedema/sangue , Polimorfismo de Fragmento de Restrição , Tireoidite Autoimune/sangueRESUMO
It has been known for a long time that there is an increased incidence of Graves' disease and immune thyroiditis in certain families. Genetic research of this disease has shown that it is most probably transmitted in a multifactorial way, i.e. that environmental as well as genetic factors play a role in the genesis of the diseases. This hypothesis is supported by the fact that the rate of concordance is maximally 50% in identical twins. The following model of threshold values is conceivable for the formal genetics of Graves' disease and immune thyroiditis: the diseases break out whenever the sum of environmental (viruses, bacteria, iodine excess, hormones, stress) and genetic (MHC and non MHC-restricted) factors is higher than a given threshold. One of the major genes influencing the genesis of the diseases seems to be HLA-DR3 (or a closely linked gene in strong linkage disequilibrium). If this gene is present, fewer environmental factors are possibly needed.
