Article
Role of anti-alpha-adrenoceptor autoantibodies and leukocytic alpha-adrenoceptors in primary Raynaud’s phenomenon
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Published: | February 5, 2019 |
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Background: α2C-adrenoceptors expressed by vascular smooth muscle cells recognize circulating norepinephrine and in this way contribute to local and systemic cold-induced vasoconstriction. Primary Raynaud’s phenomenon (pRP) is being considered as exaggerated cold-induced vasoconstriction. We hypothesize that autoantibodies targeting vascular and leukocytic α-adrenoceptor subtypes may represent a mechanism leading to pRP.
Methods: Peripheral blood and serum were obtained from patients with pRP (n=20) and age- and sex-matched healthy controls (HC, n=10). pRP was diagnosed using nailfold capillaroscopy and a questionnaire based upon published International Consensus Criteria. Circulating anti-α1/α2-adrenoceptor autoantibodies were measured by ELISA. Peripheral blood mononuclear cells (PBMC) and neutrophils (PMN) were isolated using Ficoll gradient and MACS-based separation technique, respectively. α2A, 2B, 2C-adrenoceptor mRNA and protein expressions were analyzed by qPCR and Western blot.
Results: Both, circulating anti-α1- and anti-α2-adrenoceptor autoantibodies were present in HC and patients with pRP. While the concentration of anti-α1- was higher than that of anti-α2-antibodies in HC, there were no differences between HC and pRP regarding the concentrations of anti-α1 and anti-α2-antibodies. However, clinical characteristics of pRP correlate with anti-α2-antibodies. PMN and PBMC of both, HC and patients with pRP expressed mRNA for α2A-, α2B- and α2C-adrenoceptors. In terms of protein expression an increase of α2C-adrenoceptor was observed in PMN of pRP when compared to HC. PBMC of both HC and patients with pRP showed less protein expression of α2A-, α2B- and α2C-adrenoceptors in comparison to PMN.
Conclusion: It is assumed that autoantibodies recognizing α-adrenoceptor subtypes act as ligands on these receptors and modulate the vasoconstriction of small vessels, especially in the fingers of patients with pRP leading to vasospastic episodes.