A multifaceted approach to lupus nephritis: Deciphering the interplay between adipokines, cytokines and complement...

The pro- and anti-inflammatory adipokines secreted by closely located visceral adipose tissue (VAT) have showed to modulate the inflammatory milieu around kidneys. In this study, we investigate the interplay between adipokines, cytokines and complement proteins in lupus nephritis patients.

Treatment naïve renal biopsy proven (2003 ISN/RPS) LN patients (n = 72) and healthy volunteers (n = 65) were enrolled (January 2017-January 2021). Serum adipokines, cytokines, complement proteins, C- reactive protein, Antinuclear antibodies (ANA) profile, anti-dsDNA antibodies and anti-phospholipid antibody (APA) profile were estimated using immunoassay. Serum C3 and C4 levels were measured by nephelometer.

Elevated adiponectin, adipsin, resistin, progranulin, galectin-3 and pentraxin-3 levels and reduced leptin levels were seen in LN patients when compared to healthy controls (p < 0.05). Serum IL-1β, INFγ, IL-6 and MCP-1 levels were significantly elevated whereas IL-4 levels were prominently reduced in LN patients when compared with healthy controls (p < 0.05). Serum C1q and CFP levels were significantly reduced in LN patients (p < 0.05). Elevated pentraxin-3 levels directly correlated with long disease duration and high SLEDAI score (p < 0.05). Declining renal function parameters strongly correlated with raised adiponectin, adipsin and resistin levels (p < 0.05). Adipsin levels positively correlated with complement components C3, C4 and CFB levels (p < 0.05). The PCA of serum proteins in LN patients identified three distinct clusters comprising of 37 (Cluster1), 24 (Cluster2) and 1 (Cluster3) patients in each. Adiponectin, resistin and CRP levels were found to be elevated in patients belonging to Cluster1. On the contrary, MCP1 levels were raised in Cluster2 LN patients.

The association of raised resistin, adipsin, pentraxin-3 levels with deteriorating renal function is suggestive of their potential role in LN pathogenesis. The association between adipokines and complement components indicates the regulatory role of adipokines on complements and vice versa. The identification of patient clusters based on serum protein profile indicated involvement of unique biological profiles in diverse LN pathogenesis mechanism.