Autoimmunity against the ß(2) adrenergic receptor and muscarinic-2 receptor in complex regional pain syndrome

Introduction

Complex regional pain syndrome (CRPS) is a painful condition affecting one or more extremities of the body, marked by a wide variety of symptoms and signs that are often difficult to manage because the pathophysiology is incompletely understood. A recent study showed the presence of autoantibodies against differentiated autonomic neurones in CRPS patients but it is unclear how the antibodies act in the development of CRPS. The aim of the present study was to characterise these antibodies and identify target antigens. 

Methods

Functional properties of affinity-purified immunoglobulin G of control subjects or CRPS patients were assessed using a cardiomyocyte bioassay. Putative corresponding receptors were identified using antagonistic drugs, and synthesised peptide sequences corresponding to segments of these receptors were used to identify the target epitopes. Chinese hamster ovary cells were transfected with putative receptors to ensure observed binding. Further, changes in the intracellular Ca²⁺ concentration induced by agonistic immunoglobulin G were measured using the Ca^2+-sensitive fluorescent dye fura-2 assay.

Results

The authors demonstrated the presence of autoantibodies in a subset of CRPS patients with agonistic-like properties on the ß₂-adrenergic receptor and/or the muscarinic-2 receptor. They identified these autoantibodies as immunoglobulin G directed against peptide sequences from the second extracellular loop of these receptors.

Conclusion

The authors conclude that the identification of functionally active autoantibodies in serum samples from CRPS patients supports an autoimmune pathogenesis of CRPS. They state that their findings contribute to the further understanding of this disease, and could help in the diagnosis in future and encourage new treatment strategies focusing on the immune system.