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Clinical Trial
. 2021 Jan 28:11:622326.
doi: 10.3389/fimmu.2020.622326. eCollection 2020.

C-Reactive Protein Levels in Systemic Lupus Erythematosus Are Modulated by the Interferon Gene Signature and CRP Gene Polymorphism rs1205

Helena Enocsson  1 , Birgitta Gullstrand  2 , Maija-Leena Eloranta  3 , Jonas Wetterö  1 , Dag Leonard  3 , Lars Rönnblom  3 , Anders A Bengtsson  2 , Christopher Sjöwall  1
Affiliations
Clinical Trial

C-Reactive Protein Levels in Systemic Lupus Erythematosus Are Modulated by the Interferon Gene Signature and CRP Gene Polymorphism rs1205

Helena Enocsson et al. Front Immunol. .

Abstract

Objectives: Patients with systemic lupus erythematosus (SLE) often display modest elevations of C-reactive protein (CRP) despite raised disease activity and increased interleukin (IL-) 6. We asked to what extent IL-6 levels, the CRP polymorphism rs1205, and the type I interferon (IFN) gene signature affects the basal CRP levels in patients with SLE during a quiescent phase of the disease.

Methods: CRP and IL-6 were analyzed in plasma from 57 patients meeting established classification criteria for SLE. The CRP polymorphism rs1205 was assessed and gene expression analyzed including four type I IFN-regulated genes (IGS).

Results: CRP was increased in patients with detectable IL-6 levels (p=0.001) and decreased among IGS-positive subjects (p=0.033). A multiple linear regression model revealed IL-6 to have a positive association with CRP levels, whereas both IGS-positivity and CRP genotype (rs1205) AA/GA were negatively associated with CRP-levels.

Conclusion: Our data offer an explanation to the modest CRP levels seen in viral infections and IFN-α driven autoimmunity and corroborate prior observations showing an IFN-α dependent downregulation of CRP. The latter observation, together with the fact that the CRP-lowering polymorphism rs1205 is overrepresented in human SLE, could explain low basal CRP and inadequate CRP-responses among patients with active SLE.

Keywords: C-reactive protein; biomarker; gene variants; inflammation; interferon; pentraxins; systemic lupus erythematosus; type I interferons.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Plasma CRP levels in SLE patients, and the correlation and association with plasma IL-6 concentrations (A), the IGS score measured in peripheral blood mononuclear cells (B), detectable plasma IL-6 levels (C), IGS positivity (D) and CRP rs1205 genotype (E). Dashed lines represent cut-off levels for IL-6 detection and IGS positivity, respectively.
Figure 2
Figure 2
CRP levels among patients with and without detectable IL-6 levels (Z-axis) along with different CRP genotype (rs1205) and type I IFN gene signature (IGS) status (X-axis). Bars show median values.
See this image and copyright information in PMC

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