Non-Thyroidal Immunological Abnormalities in Patients with Euthyroid Graves’ disease And Their Relatives - Abstract
Background: The ophthalmopathy associated with Graves’s hyperthyroidism, called Graves’s ophthalmopathy, is an autoimmune disorder of the extra ocular muscles and orbital connective tissue. In about 10% of patient with ophthalmopathy thyroid function tests are normal and serum thyroid antibodies are not detected. This is called “Euthyroid Graves’ Disease”. Because autoantibodies targeting the skeletal muscle protein Calsequestrin and type XIII Collagen are detected in both Graves’s ophthalmopathy and Euthyroid Graves’ Disease it might be assumed that Euthyroid Graves’ Disease is also autoimmune, although this has not been proven. Clinical Subjects and Methods: In order to test the hypothesis that Euthyroid Graves’ Disease is an autoimmune disorder, we first carried out a database search of EMBO, Google, Google scholar and PubMed for studies that looked for a personal or family history of autoimmunity, autoimmune markers such as vitiligo and alopecia or serum antibodies against autoantigens associated with various organ specific and multisystem autoimmune disorders Secondly, we studied 13 of our own patients with Euthyroid Graves’ Disease, including a patient with complex Euthyroid Graves’ Disease manifest as orbital swelling and high serum levels of Collagen XIII antibodies, for these autoimmune abnormalities We also tested their sera for Calsequestrin and type XIII collagen antibodies. Results: Data base searches showed that there have been no studies addressing the existence of non-thyroidal Immunological abnormalities, markers or autoantibodies, and their prevalences in patients with Euthyroid Graves’ Disease and their family members. In a retrospective studied of 13 of our own patients with Euthyroid Graves Diseases we found that while the prevalence of other immunological abnormalities in patients with Euthyroid Graves’ Disease was similar to than in a control group of age, but not sex matched patients with Graves Ophthalmopathy, the prevalence of immunological abnormalities in their relatives was significantly less than in relatives of patients with Graves ophthalmopathy. Discussion: While the findings in this preliminary study suggest that Euthyroid Graves’ Disease may not be an autoimmune disorder, the results are fairly weak and inconsistent with findings in an earlier study in which we reported a high prevalence of cytotoxic antibodies against fresh thyroid follicular cells and significant bands on Western blotting in many of the same patients with Euthyroid Graves’ Disease. Based on the two studies we propose that in Graves’ ophthalmopathy the primary immune reaction is in the thyroid gland land whereas in Euthyroid Graves’ Disease. The first reaction may be in the orbital tissue, the association between ophthalmopathy and thyroid autoimmunity being due to
immunological cross reactivity in both disorders. ,Conclusions: To further address the nature of, and relationship between, the orbital and thyroid reactions in Euthyroid Graves’ Disease a larger prospective study of patients
in whom B and T cell tests for immune reactivity against orbital and thyroid antigens, including the new candidate antigen IgF-1 Receptor, needs to carried out. New clinical tests for differences between Graves’s
ophthalmopathy and Euthyroid Graves’ Disease and qPCR methods to identify new thyroid and orbital shared autoantigens may provide new information about the two types of what can be called “auto-immune ophthalmopathy and its management”.