gms | German Medical Science

Introduction: Antibodies directed against G protein-coupled receptors are altered in patients with systemic sclerosis (SSc) and may serve as biomarker [1], [2]. Agonistic signaling through the β2-adrenoceptor (ADRB2) induces an anti-inflammatory response mainly via induction of IL-10 [3]. IgG with a high level of anti-ADRB2 antibodies derived from patients with chronic fatigue syndrome were linked to more TNF-α and less IL-10 production [4]. The aim of this study was to find out whether IgG with anti-ADRB2 antibodies derived from SSc patients and healthy controls (HC) alter the LPS-induced TNF-α- and IL-10 secretion by immune cells.

Methods: After pretreatment with LPS (2 ng/mL, 6 hours), peripheral blood mononuclear cells (PBMC) derived from healthy donors (n=2) were stimulated with two concentrations of protein G affinity-purified IgG (1 mg/mL; 100 µg/mL, 24 hours), derived from serum of SSc patients (n=12) and HC (n=6). The SSc patients were divided into two groups according to their anti-ADRB2 antibody values (normal: ≤10 U/ml and high: >10 U/ml). HC sera were chosen based on normal anti-ADRB2 antibody values. Anti-ADRB2 antibodies and cytokine concentrations were assessed by ELISA.

Results: SSc-IgG containing >10 U/ml anti-ADRB2 antibodies (1 mg/mL) led to increased secretion of TNF-α in comparison to LPS alone (p=0.012). No differences in TNF-α release were observed with regard to SSc-IgG containing ≤10 U/ml anti-ADRB2 antibodies or HC-IgG. Interestingly, stimulation with HC-IgG (1 mg/mL) induced a decrease in IL-10 secretion (p=0.049), when compared to LPS, while no differences were found for both groups of SSc-IgG. Although there was a tendency towards a lower IL-10 secretion after SSc-IgG containing >10 U/ml (100 μg/mL), again the differences failed to reach statistical significance. The lack of statistical significance may be due to a PBMC donor dependency of the results, which vary in terms of response to the IgG preparations.

Conclusion: The findings point towards a modulation of the inflammatory response of immune cells through anti-GPCR and maybe anti-ADRB2 antibodies in SSc. However, due to limitations of study design such as lack of specific blockade, more work is required to identify if possibly antagonistic anti-ADBR2 antibodies or other anti-GPCR antibodies play a role.

Disclosures: Mackedanz P, Graßhoff H, Lange T, Comdühr S, Müller A, Riemekasten G, Schumann A: nothing to declare

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