Date: Sunday, November 5, 2017
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.
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 September 20, 2021.
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