PGLYRP2 as a novel biomarker for the activity and lipid metabolism of systemic lupus erythematosus

Abstract

Background To assess the value of peptidoglycan recognition protein 2 (PGLYRP2) in assessing the disease activity and lipid metabolism in patients with systemic lupus erythematosus (SLE). Methods SLE patients with stable disease (n = 15), active lupus nephritis (LN) (n = 15) and neuropsychiatric systemic lupus erythematosus (NP-SLE) (n = 15) admitted to Northern Jiangsu People’s Hospital (Jiangsu, China) in 2019–2020 were recruited. In addition, volunteers with matched age and sex (n = 15) were enrolled as controls. The level of PGLYRP2 in the serum and its expression in peripheral blood mononuclear cells (PBMCs) were measured. The link between PGLYRP2 level and clinical parameters (including lipid profile) was described. Results Serum PGLYRP2 level in SLE cases exceeded that in healthy volunteers (3938.56 ± 576.07 pg/mL), and significantly higher in active LN (5152.93 ± 446.13 pg/mL) and NP-SLE patients (5141.52 ± 579.61 pg/mL). As shown by quantitative real-time PCR results, the expression of PGLYRP2 in PBMCs of SLE patients with active LN and NP-SLE surpassed that in healthy volunteers (P < 0.01). Receiver operating characteristic (ROC) curves demonstrated that PGLYRP2 was capable of distinguishing stable SLE from active LN (AUC = 0.841, 95%CI = 0.722–0.960, P = 0.000). PGLYRP2 level positively correlated with SLEDAI of SLE patients (r = 0.5783, P < 0.01). Moreover, its level varied with serological and renal function parameters (complement 3, complement 4, estimated glomerular filtration rate and 24-h urine protein) and immunoglobulin A (IgA) of SLE. A potential correlation between PGLYRP2 level and lipid profile (HLD-c, Apo-A1 and Apo B/A1) was determined in SLE patients. The linear regression analysis indicated SLEDAI as an independent factor of PGLYRP2 level, with a positive correlation in between (P < 0.05). Conclusions Serum PGLYRP2 level significantly increases in SLE patients, and is positively correlated to SLEDAI. Moreover, serum PGLYRP2 level is correlated with renal damage parameters and the abnormal lipid profile of SLE. PGLYRP2 could be used to predict SLE activity, dyslipidemia and cardiovascular disease risks in SLE patients.

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“…Of interest, a recent study also showed a positive correlation between PGLYRP2 and ApoB/A1 in patients with systemic lupus erythematosus (SLE), which suggested a potential role of PGLYRP2 in the dyslipidaemia and cardiovascular disease risks in SLE patients. 27 In the present study, no association was found between Q96PD5 and the lipid species differentially identified among groups (TG 48:0), but Q96PD5 was shown to be significantly related to A6XND0, whose gene expression (IGFBP3) was previously related to lipid metabolism. 28 In serum, IGFBP-3 is the most abundant protein of the IGFBP family that functions in an IGF-dependent (delivery of IGF and activation of IGF downstream signalling) manner, as well as in an IGF-independent (interaction with proteins) manner.…”

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“…In PMR, C3 may contribute to the inflammatory cascade leading to symptoms. Last, PGLYRP2 recognizes bacterial peptidoglycan, playing a role in innate immunity by modulating the immune response to bacterial infections [35]. In addition to its role in promoting inflammation in response to bacterial infections, PGLYRP2 has anti-inflammatory properties.…”

Diosmetin blocks type Ⅰ interferon signaling by metabolic control of phosphatidylethanolamine

“…Immunometabolism is now considered to play a key role in the pathogenesis of SLE 9,10 . Altered expression of genes controlling metabolism, such as those regulating mitochondrial function, lipid metabolism, and anaerobic glycolysis, has been documented in immune cells of SLE patients or murine lupus models, contributing to the disorder immune status [11][12][13][14] . Growing studies have illustrated that metabolites do not only act as intermediates in metabolic processes but also function as critical regulatory molecules in signal transduction 15 .…”