Antibodies against chemokine receptors CXCR3 and CXCR4 predict progressive deterioration of lung function in patients with systemic sclerosis
Abstract Background The chemokine receptors CXCR3 and CXCR4 are involved in the pathogenesis of fibrosis, a key feature of systemic sclerosis (SSc). It is hypothesized that immunoglobulin (Ig)G antibodies (abs) against these two receptors are present in patients with SSc and are associated with clin...
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doaj-f50c80a2895a44a68faedb894ed28ddd2020-11-25T00:44:50ZengBMCArthritis Research & Therapy1478-63622018-03-012011910.1186/s13075-018-1545-8Antibodies against chemokine receptors CXCR3 and CXCR4 predict progressive deterioration of lung function in patients with systemic sclerosisFlorian Weigold0Jeannine Günther1Moritz Pfeiffenberger2Otavio Cabral-Marques3Elise Siegert4Duska Dragun5Aurélie Philippe6Ann-Katrin Regensburger7Andreas Recke8Xinhua Yu9Frank Petersen10Rusan Catar11Robert Biesen12Falk Hiepe13Gerd R. Burmester14Harald Heidecke15Gabriela Riemekasten16Department of Rheumatology and Clinical Immunology, Charité University HospitalDepartment of Rheumatology and Clinical Immunology, Charité University HospitalCell Autoimmunity Group, German Rheumatism Research Center (DRFZ)Department of Rheumatology, University of LübeckDepartment of Rheumatology and Clinical Immunology, Charité University HospitalDepartment of Nephrology and Critical Care Medicine, Charité University HospitalDepartment of Nephrology and Critical Care Medicine, Charité University HospitalDepartment of Dermatology, University of LübeckDepartment of Dermatology, University of LübeckResearch Center Borstel, Airway Research Center North (ARCN), Members of the German Center for Lung Research (DZL)Research Center Borstel, Airway Research Center North (ARCN), Members of the German Center for Lung Research (DZL)Department of Nephrology and Critical Care Medicine, Charité University HospitalDepartment of Rheumatology and Clinical Immunology, Charité University HospitalDepartment of Rheumatology and Clinical Immunology, Charité University HospitalDepartment of Rheumatology and Clinical Immunology, Charité University HospitalCellTrend GmbHDepartment of Rheumatology and Clinical Immunology, Charité University HospitalAbstract Background The chemokine receptors CXCR3 and CXCR4 are involved in the pathogenesis of fibrosis, a key feature of systemic sclerosis (SSc). It is hypothesized that immunoglobulin (Ig)G antibodies (abs) against these two receptors are present in patients with SSc and are 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 enzyme-linked immunosorbent assay (ELISA). In SSc, ab levels were compared with clinical data in a cross-sectional and longitudinal setting. Protein expression of CXCR3 and CXCR4 on peripheral blood mononuclear cells (PBMCs) 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 with HD and were highest in diffuse SSc patients. The ab levels strongly correlated 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 with those with stable disease. Frequencies and median fluorescence intensities (MFI) of CXCR3+ and CXCR4+ PBMCs were lower in SSc patients compared with HD and correlated with the severity of skin and lung fibrosis. They correlated with the severity of skin and lung fibrosis. Conclusions Anti-CXCR3/4 abs and their corresponding receptors are linked with the severity of SSc-ILD. Antibody levels discriminate patients with stable or decreasing lung function and could be used for risk stratification.http://link.springer.com/article/10.1186/s13075-018-1545-8Anti-CXCR3Anti-CXCR4Systemic sclerosisInterstitial lung diseaseGPCR |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Florian Weigold Jeannine Günther Moritz Pfeiffenberger Otavio Cabral-Marques Elise Siegert Duska Dragun Aurélie Philippe Ann-Katrin Regensburger Andreas Recke Xinhua Yu Frank Petersen Rusan Catar Robert Biesen Falk Hiepe Gerd R. Burmester Harald Heidecke Gabriela Riemekasten |
spellingShingle |
Florian Weigold Jeannine Günther Moritz Pfeiffenberger Otavio Cabral-Marques Elise Siegert Duska Dragun Aurélie Philippe Ann-Katrin Regensburger Andreas Recke Xinhua Yu Frank Petersen Rusan Catar Robert Biesen Falk Hiepe Gerd R. Burmester Harald Heidecke Gabriela Riemekasten Antibodies against chemokine receptors CXCR3 and CXCR4 predict progressive deterioration of lung function in patients with systemic sclerosis Arthritis Research & Therapy Anti-CXCR3 Anti-CXCR4 Systemic sclerosis Interstitial lung disease GPCR |
author_facet |
Florian Weigold Jeannine Günther Moritz Pfeiffenberger Otavio Cabral-Marques Elise Siegert Duska Dragun Aurélie Philippe Ann-Katrin Regensburger Andreas Recke Xinhua Yu Frank Petersen Rusan Catar Robert Biesen Falk Hiepe Gerd R. Burmester Harald Heidecke Gabriela Riemekasten |
author_sort |
Florian Weigold |
title |
Antibodies against chemokine receptors CXCR3 and CXCR4 predict progressive deterioration of lung function in patients with systemic sclerosis |
title_short |
Antibodies against chemokine receptors CXCR3 and CXCR4 predict progressive deterioration of lung function in patients with systemic sclerosis |
title_full |
Antibodies against chemokine receptors CXCR3 and CXCR4 predict progressive deterioration of lung function in patients with systemic sclerosis |
title_fullStr |
Antibodies against chemokine receptors CXCR3 and CXCR4 predict progressive deterioration of lung function in patients with systemic sclerosis |
title_full_unstemmed |
Antibodies against chemokine receptors CXCR3 and CXCR4 predict progressive deterioration of lung function in patients with systemic sclerosis |
title_sort |
antibodies against chemokine receptors cxcr3 and cxcr4 predict progressive deterioration of lung function in patients with systemic sclerosis |
publisher |
BMC |
series |
Arthritis Research & Therapy |
issn |
1478-6362 |
publishDate |
2018-03-01 |
description |
Abstract Background The chemokine receptors CXCR3 and CXCR4 are involved in the pathogenesis of fibrosis, a key feature of systemic sclerosis (SSc). It is hypothesized that immunoglobulin (Ig)G antibodies (abs) against these two receptors are present in patients with SSc and are 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 enzyme-linked immunosorbent assay (ELISA). In SSc, ab levels were compared with clinical data in a cross-sectional and longitudinal setting. Protein expression of CXCR3 and CXCR4 on peripheral blood mononuclear cells (PBMCs) 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 with HD and were highest in diffuse SSc patients. The ab levels strongly correlated 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 with those with stable disease. Frequencies and median fluorescence intensities (MFI) of CXCR3+ and CXCR4+ PBMCs were lower in SSc patients compared with HD and correlated with the severity of skin and lung fibrosis. They correlated with the severity of skin and lung fibrosis. Conclusions Anti-CXCR3/4 abs and their corresponding receptors are linked with the severity of SSc-ILD. Antibody levels discriminate patients with stable or decreasing lung function and could be used for risk stratification. |
topic |
Anti-CXCR3 Anti-CXCR4 Systemic sclerosis Interstitial lung disease GPCR |
url |
http://link.springer.com/article/10.1186/s13075-018-1545-8 |
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