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The Journal of Immunology, 2000, 164: 5015-5018.
Copyright © 2000 by The American Association of Immunologists

CUTTING EDGE

Cutting Edge: A Soluble Form of CTLA-4 in Patients with Autoimmune Thyroid Disease

Martin K. Oaks1 and Karen M. Hallett

Transplant Research Laboratory and Endocrine-Diabetes Center, St. Luke’s Medical Center, and Department of Laboratory Medicine and Pathology, University of Wisconsin Medical School, Milwaukee Clinical Campus, Milwaukee, WI 53215

We have recently identified a novel transcript of the CTLA-4 gene that may represent a native soluble form of CTLA-4 (sCTLA-4). To determine whether sCTLA-4 was expressed in humans, we applied a sensitive enzyme immunoassay on serum from patients with autoimmune thyroid disease (ATD). Eleven of 20 patients with ATD had circulating levels of sCTLA-4 ranging from 28 to 78 ng/ml, whereas only 1 of 30 apparently healthy volunteers had a level greater than 4 ng/ml. sCTLA-4 immunoreactivity was inhibited by its binding to B7.1, suggesting that sCTLA-4 is a functional receptor. Immunoprecipitation analysis of serum from patients with ATD revealed a polypeptide consistent with the predicted size of sCTLA-4. We conclude that a native soluble form of CTLA-4 is derived from an alternate transcript of the CTLA-4 gene, and its level in plasma is elevated among a population of patients with ATD.




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