Abstract
BackgroundIncreased leucine-rich α2-glycoprotein-1 (LRG1) has been observed in various inflammatory and autoimmune diseases. We aimed to explore the expression and role of LRG1 in lupus nephritis (LN).MethodsPlasma LRG1 (pLRG1) was measured by enzyme-linked immunosorbent assay in 101 patients with renal biopsy-proven LN and 21 healthy controls (HC). Relationships between pLRG1 and clinical and pathological characteristics were analyzed. The expression of LRG1 in peripheral blood leukocytes and kidney was detected by flow cytometry, immunohistochemistry and immunofluorescence, respectively. Further cell experiments were focused on the role of LRG1.ResultsWe found that LRG1 was expressed in plasma, some peripheral blood leukocytes, proximal tubule and several inflammatory cells. The levels of LRG1 in plasma, peripheral blood leukocytes and kidney were elevated in LN patients as compared to HC. Plasma expression levels of LRG1 correlated positively with renal function and renal disease activity, and reflect specific pathologic lesions in the kidneys of patients with LN. Interleukin-1β and interleukin-6, not tumor necrosis factor-α and interferon γ induced the LRG1 expression in human renal tubular epithelial cell line. Moreover, stimulation of recombinant human LRG1 could inhibit late apoptosis, promote proliferation and regulate expression of inflammatory factors and cytokines.ConclusionsPlasma expression levels of LRG1 were associated with renal function, disease activity, and pathology in LN. It might also be involved in renal inflammation, proliferation and apoptosis of endothelial cells. LRG1 might be a potential prognosis novel predictor in LN patients.
Highlights
Increased leucine-rich α2-glycoprotein-1 (LRG1) has been observed in various inflammatory and autoimmune diseases
Plasma concentrations of LRG1 in healthy controls (HC) and patients with lupus nephritis (LN) For the included 101 LN patients and 21 HC, there was no statistically significant difference in the age or the sex ratio between the two groups (Table 1). Plasma LRG1 (pLRG1) levels were significantly elevated in patients with LN compared with those in the HC (P < 0.001; Fig. 1a)
Plasma concentrations of LRG1 in patients with LN according to stages of CKD All LN patients were divided into 3 groups according to stages of CKD: stage 1 (n = 58), stage 2 (n = 24) and stage 3–5 (n = 19) of CKD. pLRG1 levels were higher in all stage 1, stage 2 and stage 3–5 groups than in HC group (P < 0.05, P < 0.01 and P < 0.0001, respectively; Fig. 1b). pLRG1 levels were not significantly different between stage 1 group and stage 2 groups (P = 0.147; Fig. 1b)
Summary
Increased leucine-rich α2-glycoprotein-1 (LRG1) has been observed in various inflammatory and autoimmune diseases. We aimed to explore the expression and role of LRG1 in lupus nephritis (LN). Systemic lupus erythematosus (SLE) is a complicated and multisystem autoimmune disease [1,2,3]. Lupus nephritis (LN) is a serious and common manifestation of SLE, and is characterized by autoantibody-mediated activation of inflammatory response in the kidney [2, 4, 5]. LN is gauged by proteinuria, urinary sediment, creatinine clearance, anti-doublestanded DNA antibodies and complement component with confirmation by kidney biopsies. Yang et al BMC Nephrology (2020) 21:122 invasive nature of kidney biopsies and these traditional markers are not perfect in assessing whether active LN is present or not, and none of them can anticipate the course of LN. It is of significance to explore novel sensitive and specific biomarkers of LN
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