Coordinated Induction of Antimicrobial Response Factors in Systemic Lupus Erythematosus.

Prathapan Ayyappan,Jane H Buckner,Nora E Sarvetnick,Robert Z Harms

doi:10.3389/fimmu.2019.00658

Prathapan Ayyappan, Jane H Buckner + Show 2 more

Open Access

https://doi.org/10.3389/fimmu.2019.00658

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Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by dysregulated autoantibody production and complement activation leading to multi-organ damage. The disease is associated with increased intestinal permeability. In this study, we tested the hypothesis that SLE subjects have increased systemic exposure to bacteria. Since bacteria induce the expression of antimicrobial response factors (ARFs), we measured the levels of a series of clinically relevant ARFs in the plasma of SLE subjects. We found that levels of sCD14, lysozyme, and CXCL16 were significantly elevated in SLE subjects. A strong positive correlation was also observed between sCD14 and SELENA-SLEDAI score. Interestingly, the ratio of EndoCAb IgM:total IgM was significantly decreased in SLE and this ratio was negatively correlated with sCD14 levels. Although, there were no significant differences in the levels of lipopolysaccharide binding protein (LBP) and fatty acid binding protein 2 (FABP2), we observed significant positive correlations between lysozyme levels and sCD14, LBP, and FABP2. Moreover, galectin-3 levels also positively correlate with lysozyme, sCD14, and LBP. Since our SLE cohort comprised 43.33% males, we were able to identify gender-specific changes in the levels of ARFs. Overall, these changes in the levels and relationships between ARFs link microbial exposure and SLE. Approaches to reduce microbial exposure or to improve barrier function may provide therapeutic strategies for SLE patients.

Highlights

Systemic lupus erythematosus (SLE) is a heterogeneous chronic autoimmune disease, primarily affecting women with a gender bias of 9:1 [1]
We found a significant increase in the levels of soluble CD14 (sCD14) (P < 0.0001) in SLE patients compared to control subjects (Figure 1A)
Since we found an elevation in sCD14 in SLE patients, we asked whether sCD14 and SELENA-SLEDAI levels were correlated in SLE patients

Summary

INTRODUCTION

Systemic lupus erythematosus (SLE) is a heterogeneous chronic autoimmune disease, primarily affecting women with a gender bias of 9:1 [1]. It has been postulated that products from both Gram-negative and Gram-positive bacteria act as initiating or accelerating factors for this disease [11,12,13]. ARFs directly kill bacteria and/or activate innate immunity [18] by recruiting neutrophils and macrophages. This facilitates rapid microbial clearance, and reduces inflammation [19]. We tested the hypothesis that SLE subjects have increased exposure to bacteria. The tested factors include sCD14, lipopolysaccharide-binding protein (LBP), EndoCAb IgG, IgM, and IgA, lysozyme, galectin-3, CXCL16, and LL-37. We discovered significant correlations between lysozyme and sCD14 levels, and these factors correlated with LBP, galectin-3 and FABP2, suggesting a common stimulus

MATERIALS AND METHODS

RESULTS

DISCUSSION