RESUMO
Using a simple screening technique called regression of offspring on mid-parent (ROMP) to examine the role of IgG subclasses in affected and unaffected siblings of children and adolescents with autoimmune thyroid disease and their parents, both total-restricted and subclass-restricted autoantibodies to thyroglobulin (Tg) were assayed quantitatively for each of the IgG subclasses. There was a significant correlation of anti-Tg titer of probands with parental titers in thyrotoxicosis (TT), (R(2) = 0.569, p = 0.001), but not in chronic lymphocytic thyroiditis. The most striking correlation was in TT patients of African-American ancestry, (R(2) = 0.9863, p = 0.0007). Additional insight is provided by examining the contributions of the IgG subclasses individually, particularly those whose concentrations appear not to have direct influence on the total IgG titers. Thus, using small numbers of patients, and assaying the IgG subclass distributions, as well as any other immunoglobulin isotypes that are significantly altered in autoantibody assays, ROMP can be performed rapidly to ascertain which quantifiable parameters may be usefully extended to predict disease onset and progression.
Assuntos
Autoanticorpos/imunologia , Imunoglobulina G/imunologia , Tireoidite Autoimune/genética , Tireoidite Autoimune/imunologia , Adolescente , Criança , Feminino , Doença de Graves/imunologia , Humanos , Masculino , Tireoglobulina/imunologia , Tireotoxicose/imunologia , Adulto JovemRESUMO
Only a few methods can be applied in a simple manner to estimate the genetic control of autoimmunity in humans. Here we examined the heritability of autoantibodies to two thyroid antigens; thyroglobulin (Tg) and thyroperoxidase (TPO, formerly known as thyroid microsomal antigen), using methods of regression of offspring on mid-parental values (ROMP). With the data sets available, affected and unaffected siblings were compared by this rapid screening method using results determined by hemagglutination (HA). The presence of both types of autoantibodies showed positive heritability in patients with Graves' thyrotoxicosis (TT), but it was not observed in chronic lymphocytic or Hashimoto's thyroiditis (CLT) patients. Since these assays have been extensively used over the years by most diagnostic and research laboratories, they should provide some insight as to which quantifiable parameters may be usefully accumulated to help select groups of patients and their families for further genetic study. ROMP may also be useful to determine the sequential appearance of different types of antibody in predicting disease onset in other family members, and in distinguishing maternal and paternal effects on imprinting. The method may be extended to study epitope spreading and other measures of disease progression.
Assuntos
Autoanticorpos/sangue , Doença de Graves/genética , Doença de Graves/imunologia , Doença de Hashimoto/genética , Doença de Hashimoto/imunologia , Adolescente , Adulto , Autoanticorpos/imunologia , Autoantígenos/genética , Autoantígenos/imunologia , Criança , Família , Feminino , Humanos , Iodeto Peroxidase/genética , Iodeto Peroxidase/imunologia , Proteínas de Ligação ao Ferro/genética , Proteínas de Ligação ao Ferro/imunologia , Masculino , Análise de Regressão , Tireoglobulina/genética , Tireoglobulina/imunologia , Glândula Tireoide , Tireotoxicose/genética , Tireotoxicose/imunologiaRESUMO
The genetic control of the levels of autoantibodies has rarely been examined. We examined the heritability of autoantibodies to glutamic acid decarboxylase (GAD65) in type 1 diabetes, and to thyroglobulin (Tg) in chronic lymphocytic thyroiditis and thyrotoxicosis, using regression of offspring on midparent (ROMP) methods. Levels of autoantibodies in patients and their parents were significantly correlated in thyrotoxicosis (R2 = 0.569, p = 0.001), consistent with the reported Gm association, but not in chronic lymphocytic thyroiditis or type 1 diabetes. Extension of the procedure to other autoantibody disorders could be informative.
