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Thyrotropin receptor epitopes recognized by graves' autoantibodies developing under immunosuppressive therapy
J Wortsman1, P McConnachie, K Tahara
1Department of Medicine, Southern Illinois University School of Medicine, Springfield 62701, USA.
The Journal of Clinical Endocrinology and Metabolism
|July 14, 1998
Summary
Graves' disease can develop even with immunosuppression, characterized by specific TSH receptor autoantibodies (TSHRAbs). These autoantibodies, particularly cAMP-stimulating ones, target TSHR residues 90-165 and may indicate resistance to therapies.
Area of Science:
- Endocrinology
- Immunology
- Transplantation
Background:
- Graves' disease is an autoimmune disorder characterized by abnormal immune system modulation.
- Renal transplant recipients often require long-term immunosuppression to prevent organ rejection.
Observation:
- A renal transplant recipient on immunosuppression developed hyperthyroidism, indicative of Graves' disease.
- Despite immunosuppression, lymphocyte phenotype frequencies (CD3/DR, CD5/26, CD3/25) and a reversed CD4/CD8 ratio were consistent with Graves' disease.
- The patient's serum contained a wide spectrum of TSH receptor autoantibodies (TSHRAbs) typical of Graves' disease.
Findings:
- Stimulating TSHRAbs that increase cAMP levels were TSHR-specific, recognizing epitopes on residues 90-165.
- Other TSHRAbs and TSH binding inhibitory Igs recognized epitopes on residues 25-90.
- The cAMP-stimulating TSHRAb subtype was homogeneous, dependent on TSHR residues 90-165.
Implications:
- Graves' disease can manifest despite adequate immunosuppression in transplant recipients.
- The homogeneous cAMP-stimulating TSHRAb subtype may be linked to resistance to immunosuppressive therapy.
- Understanding TSHRAb epitope specificity is crucial for managing Graves' disease and potential therapy resistance.