Autoantibodies to the δ-opioid receptor function as opioid agonists and display immunomodulatory activity

In this report, we show that affinity purified human anti-delta opioid receptor (DOR) autoantibodies from IVIG are specific to DOR and possess agonistic properties displayed by their ability to dramatically decrease forskolin stimulated cAMP accumulation. Anti-DOR autoantibody also caused phosphorylation of the opioid receptor. Anti-DOR autoantibody treatment showed a significant reduction in CXCR4 gene expression as well as surface protein expression. In contrast, anti-DOR autoantibody treatment significantly upregulated CCR5 gene and protein expression. The presence of anti-DOR autoantibodies in IVIG and their potent immunomodulatory activity is further evidence to support the cross-talk between the neuroendocrine and immune systems.