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. 2018 Mar 12:2018:6861257.
doi: 10.1155/2018/6861257. eCollection 2018.

Monocyte Chemoattractant Protein-1 in Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis: Biomarker Potential and Association with Polymorphisms in the MCP-1 and the CC Chemokine Receptor-2 Gene

Nina Jönsson  1 , Evelina Erlandsson  1 , Lena Gunnarsson  1 , Åsa Pettersson  1 , Sophie Ohlsson  1
Affiliations

Monocyte Chemoattractant Protein-1 in Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis: Biomarker Potential and Association with Polymorphisms in the MCP-1 and the CC Chemokine Receptor-2 Gene

Nina Jönsson et al. Mediators Inflamm. .

Abstract

Antineutrophil cytoplasmic autoantibody- (ANCA-) associated vasculitis (AAV) are relapsing-remitting disorders with unpredictable prognosis. There is a need of biomarkers for distinguishing which patients will have a more severe outcome and also for predicting relapses in disease activity. This study confirms the previous results of urinary MCP-1 (uMCP-1) as a prognostic marker and explores its potential as a marker of disease activity. Method. 114 patients with AAV were followed regularly between 2002 and 2011 at Skåne University Hospital. Urine samples, blood samples, and clinical status were registered. The urine samples were analyzed in an in-house-developed ELISA. PCR-RLFP was used to analyze the MCP-1 and CCR2 genes. Results. Patients with severe prognosis had significantly higher levels of uMCP-1 compared to patients with nonsevere prognosis and healthy controls. Patients with renal damage had higher levels compared to patients who did not have renal damage. There was also a tendency of higher uMCP-1 levels in active disease as compared to remission. AA in the -2518 position in the MCP-1 gene was associated with a more severe outcome compared to the A/G or the G/G genotype. The A/A genotype were also associated with higher levels of uMCP-1. No significant associations were seen for the CCR2-V64I. Conclusion. This study confirmed the connection between high uMCP-1 levels and poor prognosis and also disease activity. It also suggests an association of the A/A genotype at position -2518 in the MCP-1 gene and poor prognosis in AAV. uMCP-1 is clearly a candidate biomarker of potential clinical value. The A/A genotype association needs further evaluation.

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Figures

Figure 1
Figure 1
Comparison of the in-house-developed ELISA and the commercial ELISA kit. The graph shows the comparison of ELISA's ability to measure determined levels of added MCP-1, the standard curve in the ELISA. Absorbance at 405 nm, background absorbance subtracted. ELISA: enzyme-linked immunosorbent assay; uMCP-1: urinary monocyte-chemoattractant protein-1.
Figure 2
Figure 2
Comparison of uMCP-1 levels in patients with severe prognosis. Nonsevere prognosis and healthy controls. Only urine samples in remission are included. All samples are divided with urinary creatinine levels. uMCP-1: urinary monocyte chemoattractant protein-1. Patients with severe prognosis had higher uMCP-1 levels (p < 0.001).
Figure 3
Figure 3
Patients who develop renal damage during the study. Longitudinal view of how uMCP-1 levels changes over time in patients who developed renal damage according to the vasculitis damage index, patients A–C. The y-axis was cut to fit in the high levels of patient B. The arrows point at the first sample taken after renal damage was discovered. Only samples in remission are included. uMCP-1 levels are divided with urinary creatinine levels. uMCP-1: urinary monocyte chemoattractant protein-1.
Figure 4
Figure 4
Patients who develop renal damage during the study. Longitudinal view of how uMCP-1 levels changes over time in patients who developed renal damage according to the vasculitis damage index, patients D–F. The y-axis was cut to fit in the high levels of patient B. The arrows point at the first sample taken after renal damage was discovered. Only samples in remission are included. uMCP-1 levels are divided with urinary creatinine levels. uMCP-1: urinary monocyte chemoattractant protein-1.
Figure 5
Figure 5
uMCP-1 levels in three of the patients who relapsed during the follow-up. All samples are taken in remission except those labelled relapse in the diagram. uMCP-1 levels are divided with urinary creatinine levels. uMCP-1: urinary monocyte chemoattractant protein-1.
Figure 6
Figure 6
Comparison of uMCP-1 levels in different disease activity. uMCP-1 levels are divided with urinary Creatinine levels. The y-axis was cut to fit in the high levels of the relapse group. uMCP-1 levels are divided with urinary creatinine levels. uMCP-1: urinary monocyte chemoattractant protein-1. uMCP-1 was higher in relapse than in remission (p < 0.05).
Figure 7
Figure 7
Comparison of uMCP-1 levels in patients with different genotype in the MCP-1 gene at position -2518. uMCP-1 levels are divided with urinary creatinine. uMCP-1 levels are divided with urinary creatinine levels. uMCP-1: urinary monocyte chemoattractant protein-1.
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