Background Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE). The pathogenesis is incompletely understood and good biomarkers for non-invasive diagnostics are scarce. Interleukin (IL)-16 is an immunomodulatory cytokine with an emerging role in SLE and LN.1–4
Aim To investigate IL-16 as a potential biomarker for LN in a well-characterized cohort of SLE patients.
Methods We measured urinary and plasma IL-16 levels in predefined patient groups: active LN (n=84), active non-renal SLE (n=63), inactive non-renal SLE (n=73) and in matched population controls (n=48) using ELISA. The LN group included patients with proliferative (PLN, n=47), mesangioproliferative (MES, n=11), and membranous (MLN, n=26) LN. Renal expression of IL-16 was investigated by immunohistochemistry (IHC). Associations between IL-16 and clinical variables and the diagnostic value of IL-16 levels for LN were explored.
Results Urinary IL-16 levels were highest among patients with LN (p<0.0001), particularly among those with PLN (p<0.035). High plasma IL-16 levels were observed in patients with active SLE, both in active renal and non-renal groups (p<0.01). In PLN, urinary IL-16 levels correlated to renal activity index (ρ=0.39, p=0.007), and albuminuria (ρ=0.31, p=0.034). IL-16 was expressed in a high proportion of cells in renal inflammatory infiltrates. In the regression models, urinary IL-16 discriminated PLN cases from all other investigated cases in the cohort (AUC=0.797, p=0.001) and other LN patients (AUC 0.775, p=0.001), while plasma IL-16 did not. Detectable urinary IL-16 had superior specificity but lower sensitivity than elevated dsDNA, low C3 or C4 for diagnosing PLN both among the whole cohort and among LN patients.
Conclusions Our data suggest that urinary IL-16 can non-invasively discriminate patients with proliferative lupus nephritis from other SLE patients. Furthermore, the abundance of IL-16 in urine and presence in kidney tissue imply a role in the pathogenesis of lupus nephritis. Its potential as a therapeutic target in SLE should be explored.
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Fava, A. et al. Urine Proteomics and Renal Single Cell Transcriptomics Implicate IL-16 in Lupus Nephritis. Arthritis Rheumatol 2021
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