Another Piece of the Puzzle of Podocyte B7-1 Expression

Lupus Nephritis

Rubina Novelli, Elena Gagliardini, Barbara Ruggiero, Ariela Benigni, Giuseppe Remuzzi

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background/Aims: Lupus nephritis (LN) is a frequent complication and a major predictor of poor prognosis of systemic lupus erythematosus. Immune complex deposition and T cell infiltration are crucial events in LN pathogenesis. B7-1 (CD80), normally expressed by antigen-presenting cells, is one of the major co-stimulators of T-cell activation through the binding with its counter-receptors CD28 and cytotoxic T-lymphocyte antigen-4. Unexpectedly, B7-1 induction was described at the podocyte level in patients affected by different renal diseases, including LN. These observations suggested a novel exciting function for B7-1 as a biomarker of podocyte injury, and hence that B7-1 inhibitory drugs could serve as podocyte-targeted treatment of intractable renal diseases. However, subsequent studies hardly questioned the reliability of B7-1 detection assays and the therapeutic efficacy of B7-1 blockade in proteinuric patients, casting doubts on B7-1 expression by podocytes. Here, we thoroughly investigated whether B7-1 was indeed expressed by podocytes in LN, before even considering employing B7-1 blockade in patients with severe manifestations of LN and unfavourable prognosis. Methods: Applying different immunohistochemical assays with 4 primary antibodies, we analysed kidney biopsies from 42 LN patients at different stages of the disease, and from NZB/NZW mice, an LN model. Results: B7-1 was not induced in podocytes in human and murine LN; instead its expression was confined to infiltrating inflammatory cells. Conclusion: B7-1 is not expressed by podocytes in LN. A renoprotective effect of B7-1 blockade in LN patients cannot be ruled out but, if confirmed, cannot be the result of an effect on podocyte B7-1.

Original languageEnglish
Pages (from-to)129-138
Number of pages10
JournalNephron
Volume133
Issue number2
DOIs
Publication statusPublished - Jun 1 2016

Fingerprint

Podocytes
Lupus Nephritis
Kidney
Inbred NZB Mouse
CTLA-4 Antigen
T-Lymphocytes
Antigen-Presenting Cells
Antigen-Antibody Complex
Systemic Lupus Erythematosus
Biomarkers
Biopsy

Keywords

  • B7-1
  • Lupus nephritis
  • Podocyte

ASJC Scopus subject areas

  • Physiology
  • Nephrology
  • Urology
  • Physiology (medical)

Cite this

Another Piece of the Puzzle of Podocyte B7-1 Expression : Lupus Nephritis. / Novelli, Rubina; Gagliardini, Elena; Ruggiero, Barbara; Benigni, Ariela; Remuzzi, Giuseppe.

In: Nephron, Vol. 133, No. 2, 01.06.2016, p. 129-138.

Research output: Contribution to journalArticle

Novelli, Rubina ; Gagliardini, Elena ; Ruggiero, Barbara ; Benigni, Ariela ; Remuzzi, Giuseppe. / Another Piece of the Puzzle of Podocyte B7-1 Expression : Lupus Nephritis. In: Nephron. 2016 ; Vol. 133, No. 2. pp. 129-138.
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