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Parathyroid Hormone Resistance and Autoantibodies to the PTH1 Receptor
Adel Mandl1, Peter D Burbelo1, Giovanni Di Pasquale1
1From the Metabolic Diseases Branch (A.M., J.W., W.F.S., S.K.A., J.E.B., L.S.W.) and the Kidney Diseases Branch (M.A.W., J.E.B.), National Institute of Diabetes and Digestive and Kidney Diseases, the Adeno-Associated Virus Biology Section (P.D.B., G.D.P., J.A.C.), Salivary Disorders Unit (B.M.W.), and Skeletal Disorders and Mineral Homeostasis Section (M.T.C.), National Institute of Dental and Craniofacial Research, the Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (M.S.L.), the Symptom Management Branch, National Institute of Nursing Research (B.W.), and the Department of Laboratory Medicine, Clinical Center (S.D.R.), National Institutes of Health, Bethesda, MD; and Kaiser Permanente, Sacramento, CA (Y.S.T.).
Two patients developed resistance to parathyroid hormone (PTH) due to autoantibodies blocking the PTH type 1 receptor (PTH1R). These findings highlight a novel autoimmune mechanism affecting calcium regulation.
Area of Science:
- Endocrinology
- Immunology
- Nephrology
Background:
- Parathyroid hormone (PTH) is crucial for calcium homeostasis.
- PTH resistance can lead to dysregulation of calcium metabolism.
- Autoimmune conditions can manifest with diverse clinical presentations.
Observation:
- Two cases of acquired resistance to parathyroid hormone (PTH) were identified.
- Both cases involved the development of serum autoantibodies targeting the PTH type 1 receptor (PTH1R).
- These autoantibodies were found to block PTH binding and signaling.
Findings:
- In vitro assays confirmed the presence of PTH1R-blocking IgG autoantibodies in affected patients.
- The autoantibodies specifically inhibited PTH's ability to bind and signal through PTH1R.
- These blocking autoantibodies were absent in control groups with other renal or autoimmune disorders.
Implications:
- This study identifies a novel autoimmune mechanism causing acquired PTH resistance.
- The findings suggest a potential link between autoimmune disorders and impaired calcium regulation via PTH1R.
- Understanding these autoantibodies may inform future diagnostic and therapeutic strategies for related conditions.
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