Abstract
ObjectivesPatients 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.MethodsCRP 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).ResultsCRP 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.ConclusionOur 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.
Highlights
The acute-phase protein C-reactive protein (CRP) is a key actor in the clearance of bacteria and dying cells
Modest CRP-responses are recorded in autoimmune diseases characterized by increased type I interferon (IFN) activity, e.g., systemic lupus erythematosus (SLE) [8], and lack of correlation between IL-6 and CRP has been demonstrated in patients with SLE [10]
CRP Is Associated With IL-6 and IFN gene signature (IGS)-Status
Summary
The acute-phase protein C-reactive protein (CRP) is a key actor in the clearance of bacteria and dying cells. Its pentameric structure encompasses an effector face with affinity for C1q and Fcgreceptors and a recognition face with the ability to bind phosphocholine on e.g., dying cells and pathogens, and nuclear constituents exposed during apoptosis (i.e., snRNP and histones) [1, 2]. These qualities enable CRP to contribute to efficient clearance of cell remnants and immune complexes by complement activation/modulation, opsonization, and phagocytosis, biological processes considered dysfunctional in systemic lupus erythematosus (SLE) [3, 4]. Type I IFNs are strong activators of the anti-viral immune response, but may contribute to autoantibody production in several autoimmune conditions [11]
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