Impaired catecholaminergic signalling of B lymphocytes in patients with chronic rheumatic diseases
- aClinic of Medicine and Polyclinic IV, University of Leipzig, Germany, bDepartment of Medicine, Medicine Polyclinic, Philipps University of Marburg, Germany, cDepartment of Medicine, Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany
- Dr M Wahle, University of Leipzig, Clinic of Medicine and Polyclinic IV, Härtelstrasse 16–18, D-04107 Leipzig, Germany
- Accepted 18 September 2000
OBJECTIVE To investigate further the influence of the autonomic nervous system on chronic rheumatic diseases.
METHODS The density and affinity of β2 adrenergic receptors (β2R) on CD19+ lymphocytes in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc), as well as intracellular cAMP levels in patients with RA and SLE, were determined. Human peripheral blood mononuclear cells were separated from venous blood of patients and healthy controls by Ficoll-Hypaque density centrifugation. CD19+ lymphocytes were purified by magnetic cell sorting, and β2R were determined by a radioligand binding assay with [125I]iodocyanopindolol. Intracellular cAMP levels and β2R agonist induced cell death were measured by a radioimmunoassay and flow cytometry using annexin-V binding, respectively. Systemic disease activity of the patients was evaluated using multifactorial scoring systems.
RESULTS The density of β2R on peripheral CD19+ lymphocytes was significantly decreased in patients with RA, SLE, and SSc compared with healthy controls. In patients with RA and SSc β2R density was negatively correlated 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 β2R was significantly reduced in these patients compared with control subjects. Preliminary data suggest that β2R agonist induced cell death is diminished in patients with RA exhibiting decreased β2R densities.
CONCLUSIONS The results of this study show a reduction of β2R 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.