Impaired catecholaminergic signalling of B lymphocytes in patients with chronic rheumatic diseases

Objective-To investigate further the influence of the autonomic nervous sys tem on chronic rheumatic diseases. Methods-The density and affinity of beta (2) adrenergic receptors (beta 2R) on CD19+ lymphocytes in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc), as well as intrace llular cAMP levels in patients with RA and SLE, were determined. Human peri pheral blood mononuclear cells were separated from venous blood of patients and healthy controls by Ficoll-Hypaque density centrifugation. CD19+ lymph ocytes were purified by magnetic cell sorting, and beta 2R were determined by a radioligand binding assay with [I-125]iodocyanopindolol. Intracellular cAMP levels and beta 2R agonist induced cell death were measured by a radi oimmunoassay and flow cytometry using annexin-V binding, respectively. Syst emic disease activity of the patients was evaluated using multifactorial sc oring systems. Results-The density of beta 2R on peripheral CD19+ lymphocytes was signific antly decreased in patients with RA, SLE, and SSc compared with healthy con trols. In patients with RA and SSc beta 2R density was negatively correlate d with systemic disease activity. Furthermore, although basal intracellular cAMP levels were raised in patients with RA and SLE, the increase of cAMP upon stimulation of beta 2R was significantly reduced in these patients com pared with control subjects. Preliminary data suggest that beta 2R agonist induced cell death is diminished in patients with RA exhibiting decreased b eta 2R densities. Conclusions-The results of this study show a reduction of beta 2R densities on B lymphocytes mirrored by an impaired intracellular cAMP generation in patients with chronic rheumatic diseases, indicating a decreased influence of the autonomic nervous system on B cells in these conditions.