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. 2001 May;60(5):505–510. doi: 10.1136/ard.60.5.505

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

M Wahle 1, S Kolker 1, A Krause 1, G Burmester 1, C Baerwald 1
PMCID: PMC1753636  PMID: 11302874

Abstract

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.



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Figure 1  .

Figure 1  

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Density of β2 adrenergic receptors (β2R) on CD19+ lymphocytes. The density of β2R on CD19+ cells is significantly reduced in patients with chronic rheumatic diseases (rheumatoid arthritis (RA, n=24), systemic lupus erythematosus (SLE, n=13), systemic sclerosis (SSc, n=6) compared with healthy control subjects (controls, n=16) (p<0.001; one way analysis of variance followed by Tukey's procedure; RA, SLE, or SSc v controls). No significant difference is seen between the three patient groups. Data are presented as plots of the receptor numbers of individual subjects, the bar representing the mean.

Figure 2  .

Figure 2  

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Correlation of the density of β2 adrenergic receptors (β2R) with disease activity. In patients with rheumatoid arthritis (RA) and systemic sclerosis (SSc) a significant negative correlation could be seen between systemic activity scores and the density of β2R on CD19+ lymphocytes. Correlation between β2R and disease activity just missed the significance level in the group with SLE: (A) β2R v the total disease activity score (TAI) in patients with RA; (B) β2R v the SLE activity measure (SLAM) in patients with SLE; (C) β2R v the SSc score (SSS) in patients with SSc. Correlation between β2R and the values obtained by the different scoring systems used in this study (TAI, SLAM, SSS) was calculated by the Pearson product moment correlation test.

Figure 3  .

Figure 3  

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Intracellular cAMP levels. Basal cAMP levels (cAMP basal) were significantly raised in patients with systemic lupus erythematosus (SLE) compared with control subjects. The relative increase of cAMP (% increase cAMP) above basal levels after isoprenaline stimulation was markedly decreased in both patient groups compared with the control group (* p<0.05, ** p<0.001; one way analysis of variance followed by Tukey's procedure; RA, SLE v control).

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