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Introduction: Autoantibodies (abs) targeting G protein-coupled receptors (GPCR), growth factors (GF) and their receptors (GFR) may play a role in the pathogenesis of systemic sclerosis (SSc). Previous research by Sterner et al. evaluated 28 different abs and identified beta-adrenergic receptor 1 (ADRB1), fibroblast growth factor (FGF2), and placental growth factor (PlGF) as the most distinguishing markers separating systemic sclerosis (SSc) patients from healthy control (HC) [1].

This study aims to investigate the specificity of abs against ADRB1, FGF2, and PlGF in systemic sclerosis compared to HC and other rheumatic autoimmune diseases.

Methods: Serum levels of abs against FGF2, ADRB1, and PlGF were measured by ELISA in participants with SSc (n=132), rheumatoid arthritis (RA, n=39), ANCA-associated vasculitis (AAV, n=67), connective tissue disease (CTD, n=109), and HC (n=29).

To analyze differences in ab levels, the student’s t-test was applied – both to compare cohorts (SSc, RA, AAV, CTD, HC) and subgroups within cohorts, as well as to assess differences between patients with and without interstitial lung disease (ILD). Additionally, predictive ability of the abs to distinguish between SSc and non-SSc individuals was evaluated using Receiver Operating Characteristic (ROC). The area under the curve (AUC) was estimated to assess the abs’ performance with a 95% confidence interval (CI).

Results: Comparison of ab levels between the cohorts showed significantly increased PlGF-ab values (p<0.001) in SSc compared to RA, AAV, CTD, and HC. An estimated AUC of 0.833 was observed, showing substantial discriminatory ability of PlGF-ab between SSc and non-SSc individuals (RA, AAV, CTD, HC). PlGF-ab levels were significantly elevated in ILD patients (p<0.001), suggesting a potential profibrotic role of PlGF-ab in pulmonary fibrosis.

ADRB1-ab showed the highest levels in CTD (p<0.001) compared to SSc, RA, AAV, and HC. However, SSc still showed significantly higher ab levels (p<0.001) than RA, AAV, and HC. ADRB1-ab demonstrated high prediction performance to distinguish between SSc and non-SSc individuals (RA, AAV, HC), with an AUC of 0.873 in the ROC analysis when CTD cohort was excluded.

FGF2-ab levels were highest in the healthy control group (p < 0.001).

Conclusion: This study demonstrates that abs against PlGF, ADRB1, and FGF2 exhibit distinct expression patterns across different rheumatic autoimmune disease cohorts. Especially PlGF-ab showed strong discriminatory power between SSc and non-SSc individuals while also being associated with ILD manifestation. Further studies are needed to explore the mechanistic role of these abs in SSc pathogenesis.

References