Analysis of proteins immunoprecipitated from plasma donated by patients with autoimmune disease with a pool of anti–CTLA-4 Abs specific for the N-terminal CD80/CD86 binding domain of CTLA-4 has shown that the isolated molecules exhibited characteristics common to Igs and were able to interact with CD80 and CD86 ligands, but did not have the sequence of an isoform of CTLA-4 (26). Here, CTLA4 is linked to autoimmune disease.