Serum Interleukin-34 Levels Are Elevated in Patients with Systemic Lupus Erythematosus

Abstract

Interleukin-34 (IL-34) was initially identified as an alternative ligand for the colony-stimulating factor-1 receptor (CSF-1R) to mediate the biology of mononuclear phagocytic cells. Recently, IL-34 was found to be associated with chronic inflammation, such as in rheumatoid arthritis (RA). Both RA and systemic lupus erythematosus (SLE) are multifactorial autoimmune diseases and are characterized by excessive immune and inflammatory responses. Thus, we investigated whether IL-34 is involved in the pathogenesis of SLE. In all, 78 SLE patients and 53 healthy controls were enrolled in the research. Enzyme-linked immunosorbent assay (ELISA) was employed to measure the concentrations of serological IL-34. Then serum IL-34 levels between the SLE group and healthy controls were analyzed by the Mann-Whitney U test. Meanwhile, the correlations between the serum IL-34 levels and disease activity indexes and other established serum markers were assessed. Furthermore, the serum IL-34 levels of 20 active SLE patients were reevaluated when diseases were in the remission stage from corticosteroids or immunosuppressive drugs. Serum IL-34 levels were significantly higher in SLE patients compared to healthy controls. Their levels were remarkably associated with accumulation of the clinical features of SLE. Additionally, IL-34 titers were positively correlated with the SLE disease activity indexes, anti-double-stranded DNA antibody (anti-dsDNA) titers and C-reactive protein (CRP) levels, and inversely with complement3 (C3) levels. Moreover, serum IL-34 levels were significantly decreased after successful treatment of SLE. Serum IL-34 could be a candidate biomarker for SLE as there are elevated serum levels in treatment-naive SLE patients and we saw a significant decrease after effective treatment.

The roles of CSFs on the functional polarization of tumor‐associated macrophages

“…In contrast to M-CSF, IL-34 is undetectable in the serum of healthy subjects [23]. An overexpression of IL-34 has been reported in some severe diseases associated with chronic inflammation, such as viral infections [37,77], inflammatory bowel diseases [78], rheumatoid arthritis [76,79], systemic lupus erythematosus [80], and Sjogren's syndrome [81]. In contrast, one study has reported a decrease in IL-34 expression in patients chronically infected by hepatitis B virus [82].…”

Serum interleukin‐34 levels in patients with systemic sclerosis: Clinical association with interstitial lung disease

“…Importantly, IL‐34 is induced at protein level under inflammatory conditions including autoimmune diseases. Indeed, several studies have shown that serum IL‐34 levels are increased in rheumatoid arthritis and systemic lupus erythematosus . Furthermore, recent studies have demonstrated that IL‐34 promotes the differentiation of monocytes into profibrotic macrophages .…”

“…Indeed, several studies have shown that serum IL-34 levels are increased in rheumatoid arthritis and systemic lupus erythematosus. 5,6 Furthermore, recent studies have demonstrated that IL-34 promotes the differentiation of monocytes into profibrotic macrophages. 7 Consistent with this, serum IL-34 levels correlate with the severity of liver fibrosis in patients with chronic hepatitis C, where macrophages acquire profibrotic properties.…”

Serum levels of interleukin‐34 and clinical correlation in patients with primary Sjögren's syndrome

“…Some studies concerning IL‐34 in connective tissue diseases (CTDs) have been reported. It has been shown that serum IL‐34 levels were elevated in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), as well as systemic sclerosis (SSc), and were associated with disease activity to varying degrees . As a member of the CTDs, pSS was also revealed to be associated with IL‐34, and it was shown that IL‐34 messenger RNA (mRNA) was significantly up‐regulated in the inflamed salivary glands of patients with pSS and associated with local expansion of pro‐inflammatory CD14 bright CD16 + monocytes .…”

“…It has been shown that serum IL-34 levels were elevated in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), as well as systemic sclerosis (SSc), and were associated with disease activity to varying degrees. [12][13][14][15][16] As a member of the CTDs, pSS was also revealed to be associated with IL-34, and it was shown that IL-34 messenger RNA (mRNA) was significantly up-regulated in the inflamed salivary glands of patients with pSS and associated with local expansion of pro-inflammatory CD14 bright CD16 + monocytes. 10 However, the role of IL-34 in the peripheral blood of patients with pSS and how it might correlate with clinical parameters are still unknown.…”