Impaired catecholaminergic signalling of B lymphocytes in patients with chronic rheumatic diseases.
OBJECTIVE
To investigate further the influence of the autonomic nervous system on chronic rheumatic diseases.


METHODS
The density and affinity of beta2 adrenergic receptors (beta2R) 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 beta2R were determined by a radioligand binding assay with [125I]iodocyanopindolol. Intracellular cAMP levels and beta2R 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 beta2R on peripheral CD19+ lymphocytes was significantly decreased in patients with RA, SLE, and SSc compared with healthy controls. In patients with RA and SSc beta2R 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 beta2R was significantly reduced in these patients compared with control subjects. Preliminary data suggest that beta2R agonist induced cell death is diminished in patients with RA exhibiting decreased beta2R densities.


CONCLUSIONS
The results of this study show a reduction of beta2R 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.
Wahle
M
M
Clinic of Medicine and Polyclinic IV, University of Leipzig, Germany. wahm@medizin.uni-leipzig.de
Kölker
S
S
Krause
A
A
Burmester
G R
GR
Baerwald
C G
CG
D000328:Adult; D000368:Aged; D018941:Antigens, CD19; D001172:Arthritis, Rheumatoid / Q000276:immunology; D001402:B-Lymphocytes / Q000378:metabolism*; D016022:Case-Control Studies; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018343:Receptors, Adrenergic, beta-2 / Q000032:analysis*; D012216:Rheumatic Diseases / Q000276:immunology*; D012595:Scleroderma, Systemic / Q000276:immunology; D015398:Signal Transduction
D018941:Antigens, CD19; D018343:Receptors, Adrenergic, beta-2; D000242:Cyclic AMP