Perspective | Published:

OPINION

The role of B7-1 in proteinuria of glomerular origin

Nature Reviews Nephrology (2018) | Download Citation

Abstract

The damage and loss of podocytes is a primary hallmark of nephrotic syndrome. In the pursuit of targetable molecules that are involved in podocyte pathophysiology, some studies have identified B7-1 (also known as CD80) as a potential biomarker. Furthermore, B7-1 blockade has been proposed as a podocyte-specific treatment for patients with nephrotic syndrome who have limited therapeutic options, such as those with focal segmental glomerulosclerosis, minimal change disease, diabetic nephropathy and lupus nephritis. In this Perspectives article, we describe and compare supporting and contradicting data on the role of podocyte B7-1 in the pathogenesis of various podocytopathies. Moreover, we highlight crucial issues that should be addressed urgently — such as standardization of sample processing time, material conservation and antibody usage in immunohistochemical protocols — as a clinical trial that is investigating the efficacy of B7-1 blockade in treatment-resistant nephrotic syndrome is ongoing.

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Acknowledgements

The authors thank K. Mierke, IRCCS–Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy, for editing the manuscript before submission. R.N. is a recipient of a fellowship from ‘Fondazione Aiuti per la Ricerca sulle Malattie Rare (ARMR)’, Bergamo, Italy.

Author information

Affiliations

  1. IRCCS–Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy

    • Rubina Novelli
    • , Ariela Benigni
    •  & Giuseppe Remuzzi
  2. Unit of Nephrology and Dialysis, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy

    • Giuseppe Remuzzi
  3. ‘L. Sacco’ Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy

    • Giuseppe Remuzzi

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Contributions

R.N. and G.R. wrote the manuscript; A.B. and G.R. critically revised the paper. All authors reviewed and approved the final manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Giuseppe Remuzzi.

Glossary

CTLA4-immunoglobulin fusion protein

(CTLA4-Ig). A soluble protein chimaera that consists of the extracellular domain of CTLA4 fused to the crystallizable fragment (Fc) portion of human IgG1.

Microbead-mediated crosslinking

A laboratory technique that uses uniform polymer particles to bind and isolate specific targets.

MRL-Faslpr mice

Lupus-prone mice that develop a systemic autoimmune syndrome that shares many features with human systemic lupus erythematosus.

Polyinosinic:polycytidylic acid

(polyIC). Toll-like receptor 3 (TLR3) ligand that has structural similarities with double-stranded DNA. polyIC is used for the induction of podocytopathy and proteinuria.

Synaptopodin

Actin-associated protein that is expressed by renal podocytes.

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https://doi.org/10.1038/s41581-018-0037-z