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Abstract Number: 724

Antibodies Against the Chemokine Receptors CXCR3 and CXCR4 Predict Progressive Lung Fibrosis in Systemic Sclerosis (SSc)

Gabriela Riemekasten1, Elise Siegert2 and Harald Heidecke3, 1Department of Rheumatology, Universitatsklinikum Schleswig-Holstein, Lubeck, Germany, 2Rheumatology and Clinical Immunology, University Hospital Charité, Berlin, Germany, 3CellTrend GmbH Luckenwalde, Luckenwalde, Germany

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: autoantibodies, Biomarkers, Chemokine Receptors, fibrosis and systemic sclerosis

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Session Information

Date: Sunday, November 5, 2017

Title: Systemic Sclerosis, Fibrosing Syndromes and Raynaud's – Clinical Aspects and Therapeutics Poster I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Chemokine receptors CXCR3 and CXCR4 are involved in immune cell migration and in the pathogenesis of inflammatory fibrosis, a key feature of systemic sclerosis (SSc). It is hypothesized that IgG antibodies (ab) against these two receptors are present in patients with SSc and associated with clinical findings.

Methods: Anti-CXCR3 and anti-CXCR4 ab levels were measured in 449 sera from 327 SSc patients and in 234 sera from healthy donors (HD) by ELISA. In SSc, ab levels were compared with clinical data in a cross-sectional and longitudinal setting. Protein expression of CXCR3 and CXCR4 on PBMC was analyzed in 17 SSc patients and 8 HD by flow cytometry.

Results: Anti-CXCR3 and anti-CXCR4 ab levels were different among SSc subgroups compared to HD and were highest in diffuse SSc patients. The ab levels strongly correlate with each other (r = 0.85). Patients with SSc-related interstitial lung disease (SSc-ILD) exhibited higher ab levels, which negatively correlated with lung function parameters (e.g. r = -0.5 and r = -0.43 for predicted vital capacity, respectively). However, patients with deterioration of lung function showed lower anti-CXCR3/4 ab levels compared to those with stable disease. Frequencies and median fluorescence intensities (MFI) of CXCR3+ and CXCR4+ PBMC were lower in SSc patients compared to HD. They correlated with the severity of skin and lung fibrosis (Fig. 1).

Fig. 1: Frequency of CXCR3-positive CD14+ monocytes among CD14+ monocytes (a) as well as CXCR3 density (b) on CD14+ monocytes negatively correlated with the predicted percentages of forced vital capacity (FVC). (c) CXCR4 density on CD4+ T cells correlated with modified Rodnan skin score (mRSS).

Conclusion: Anti-CXCR3/4 ab and their corresponding receptors are linked with severity of lung fibrosis. High ab levels could serve as marker for SSc-ILD stability suggesting a protective role of these ab in SSc-ILD.


Disclosure: G. Riemekasten, CellTrend, 4; E. Siegert, None; H. Heidecke, Heideckes, 4,Riemekasten, 4.

To cite this abstract in AMA style:

Riemekasten G, Siegert E, Heidecke H. Antibodies Against the Chemokine Receptors CXCR3 and CXCR4 Predict Progressive Lung Fibrosis in Systemic Sclerosis (SSc) [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/antibodies-against-the-chemokine-receptors-cxcr3-and-cxcr4-predict-progressive-lung-fibrosis-in-systemic-sclerosis-ssc/. Accessed .
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