The costimulatory receptor B7-1 is not induced in injured podocytes

Abstract

Recent research on podocytes has proposed B7-1 as an important player in podocyte biology and as a potential new therapeutic target. B7-1 was upregulated in injured podocytes and described as a biomarker to identify patients who may benefit from abatacept, a B7-1 blocker. However, after this initial enthusiasm, several reports have not confirmed the efficiency of abatacept at inducing proteinuria remission in patients. In order to resolve these discrepancies, we explored the role of B7-1 in the injured podocyte. Both primary cultured and immortalized podocytes were exposed to lipopolysaccharides, but this failed to induce B7-1 expression at the mRNA and protein levels. Importantly, TLR-4 engagement confirmed lipopolysaccharide efficacy. We then evaluated B7-1 expression in several mouse models of podocyte injury including treatment with lipopolysaccharide or Adriamycin, a lupus prone model (NZB/W F1) and subtotal nephrectomy. Using 3 commercially available anti-B7-1 antibodies and appropriate controls, we could not find B7-1 expression in podocytes, whereas some infiltrating cells were positive. Thus, our findings do not support a role for B7-1 in podocyte biology. Hence, further studies are mandatory before treating proteinuric patients with B7-1 blockers.

Febrile Proteinuria in Hospitalized Children: Characterization of Urinary Proteins

“…Yu et al showed the resolution of nephrotic range proteinuria after B7-1 inhibition with Abatacept (CTLA-4–Ig) treatment in patients with rituximab-resistant recurrent FSGS and in patients with glucocorticoid-resistant primary FSGS ( 18 ), suggesting that B7-1 can be a target for the treatment of proteinuria. However, these findings have recently been challenged by Baye et al ( 19 ). These new observations led us to explore the possible role of B7-1 in febrile children.…”

Role of Podocyte Injury in Glomerulosclerosis

“…It has been found that B7-1 was expressed on podocytes of lupus nephritis (LN) (Reiser et al 2004), and the expression of podocyte B7-1 in LN patients and LN mouse models is positively correlated with the degree of proteinuria. However, new evidence has stricken up a discordant tune (Baye et al 2016), leading to further mandatory studies of the application of B7-1 blockers in treating proteinuric patients (Novelli et al 2016a).…”

Podocyte Injury in Lupus Nephritis

“…Moreover B7-1 (CD80), which is usually expressed on B cells and APCs and induces T-cell co-stimulation, has also been detected on podocytes in several models of proteinuric kidney diseases, including LN [76]. However, recent studies have reported conflicting results suggesting that B7-1 is not expressed in mouse models of LN and in human LN [77,78]. Moreover, clinical trials in patients with LN failed to demonstrate a clear outcome benefit of abatacept, an inhibitor of B7-1/CD28 interaction [79,80].…”