Cutting edge: a soluble form of CTLA-4 in patients with autoimmune thyroid disease.
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.
Oaks
M K
MK
Transplant Research Laboratory and Endocrine-Diabetes Center, St. Luke's Medical Center, Department of Laboratory Medicine and Pathology, University of Wisconsin Medical School, Milwaukee Clinical Campus, Milwaukee, WI 53215, USA. Moaks@execpc.com
Hallett
K M
KM
D000069594:Abatacept; D000328:Adult; D000911:Antibodies, Monoclonal / Q000097:blood; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000097:blood* / Q000276:immunology; D018122:B7-1 Antigen / Q000235:genetics; D001667:Binding, Competitive / Q000276:immunology; D060908:CTLA-4 Antigen; D005260:Female; D006801:Humans; D018796:Immunoconjugates; D007124:Immunoenzyme Techniques; D007141:Immunoglobulin Fc Fragments / Q000235:genetics; D007166:Immunosuppressive Agents / Q000037:antagonists & inhibitors / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000494:pharmacology; D012995:Solubility; D013967:Thyroiditis, Autoimmune / Q000097:blood / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D007141:Immunoglobulin Fc Fragments; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D000069594:Abatacept