Interleukin (IL) 16: a candidate urinary biomarker for proliferative lupus nephritis

Abstract

ObjectiveLupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE). The pathogenesis is incompletely understood and diagnostic biomarkers are scarce. We investigated interleukin (IL) 16 as a potential biomarker for LN in a well-characterised cohort of patients with SLE.MethodsWe measured urinary (u-) and plasma (p-) levels of IL-16 in predefined patient groups using ELISA: LN (n=84), active non-renal SLE (n=63), inactive non-renal SLE (n=73) and matched population controls (n=48). The LN group included patients with recent biopsy-confirmed proliferative (PLN, n=47), mesangioproliferative (MES, n=11) and membranous (MLN, n=26) LN. Renal expression of IL-16 was investigated by immunohistochemistry. Associations between IL-16 measurements and clinical parameters and the diagnostic value for LN were explored.Resultsp-IL-16 was detected in all investigated cases and high p-IL-16 levels were observed in patients with active SLE. u-IL-16 was detected (dt-u-IL-16) in 47.6% of patients with LN, while only up to 17.8% had dt-u-IL-16 in other groups. In the LN group, 68% of patients with PLN had dt-u-IL-16, while the proportions in the MLN and MES groups were lower (11.5% and 45.5%, respectively). The highest u-IL-16 levels were detected in the PLN group. In the regression model, u-IL-16 levels differentiated PLN from other LN patient subgroups (area under the curve 0.775–0.896, p<0.0001). dt-u-IL-16 had superior specificity but slightly lower sensitivity than elevated anti-double-stranded DNA and low complement C3 or C4 in diagnosing PLN. A high proportion of LN kidney infiltrating cells expressed IL-16.ConclusionsWe demonstrate that detectable u-IL-16 can differentiate patients with PLN from those with less severe LN subtypes and active non-renal SLE. Our findings suggest that u-IL-16 could be used as a screening tool at suspicion of severe LN. Furthermore, the high IL-16 levels in plasma, urine and kidney tissue imply that IL-16 could be explored as a therapeutic target in SLE.

Single cell spatial transcriptomic profiling of childhood-onset lupus nephritis reveals complex interactions between kidney stroma and infiltrating immune cells

“…In contrast, B.3 cells with higher expression of IL16 were more likely to interact with CD8 + memory T cells, regulatory T cells, and other B cells ( Fig. 4H ), a notable finding given recent reports identifying urine IL-16 as a biomarker of LN disease activity ( 32, 33 ). Together with our spatial network analyses ( Fig.…”

Urine proteomic signatures of histological class, activity, chronicity, and treatment response in lupus nephritis

“…Here, we validated this finding, applying an unbiased approach in an independent larger cohort of LN patients, corroborating the role of IL-16 as a biomarker and in LN pathogenesis. The association of urinary IL-16 with active proliferative LN was also validated in an independent Swedish cohort (33). IL-16 is a proinflammatory chemokine that can activate and recruit CD4+ and CD9+ cells (34)(35)(36)(37).…”

Systemic lupus erythematosus: one year in review 2023

“…Also, interleukin-6 was higher in the plasma of patients with active SLE in comparison with quiescent cases (11). The levels of a number of other biomarkers correlated with renal involvement, for instance, urinary IL-16 (u-IL-16) was higher in patients with active lupus nephritis and may be useful in differentiating patients with proliferative lupus nephritis from those with less severe LN subtypes and urinal SLE (11).…”