title: Any value of podocyte B7-1 as a biomarker in human MCD and FSGS?
abstract: Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are the most common causes of nephrotic syndrome in children and in young adults. Relapsing MCD carries the risk of severe complications and prolonged immunosuppression, whereas FSGS remains largely untreatable and urgently needs more effective treatments. Recently, induction of B7-1 (CD80), an immune-related protein expressed by antigen-presenting cells, was observed in podocytes of MCD and FSGS patients, suggesting that B7-1 plays a role in the pathogenesis of these diseases, and hence that abatacept, a B7-1 inhibitor, could be a possible treatment. Since previous studies raised serious concerns regarding the reliability of immunohistochemical assays for B7-1 detection and the efficacy of B7-1 inhibitory treatment, we investigated B7-1 podocyte expression in MCD and FSGS patients. Using different primary antibodies and immunohistochemical assays, no significant upregulation of podocyte B7-1 was detected in patients' biopsies compared with controls. To further confirm our findings, we analyzed mice with adriamycin-induced nephropathy, a model of human FSGS, and mice injected with LPS as additional control. Podocyte B7-1 was not observed in mice injected with adriamycin or LPS either. In conclusion, since B7-1 is not induced in podocyte of MCD and FSGS patients, the antiproteinuric action of abatacept, if confirmed, may not be the result of an effect on podocyte B7-1.
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy;
authors.forename: Rubina
authors.initials: R
authors.lastname: Novelli
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy;
authors.forename: Elena
authors.initials: E
authors.lastname: Gagliardini
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy;
authors.forename: Barbara
authors.initials: B
authors.lastname: Ruggiero
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy; ariela.benigni@marionegri.it.
authors.forename: Ariela
authors.initials: A
authors.lastname: Benigni
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy; Unit of Nephrology and Dialysis, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy; and Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D018122:B7-1 Antigen / Q000032:analysis*; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D004195:Disease Models, Animal; D004317:Doxorubicin; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000139:chemically induced / Q000175:diagnosis / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009402:Nephrosis, Lipoid / Q000175:diagnosis / Q000378:metabolism*; D050199:Podocytes / Q000737:chemistry*; D011237:Predictive Value of Tests; D055815:Young Adult
chemical_list: D018122:B7-1 Antigen; D015415:Biomarkers; D004317:Doxorubicin
keywords: B7-1; focal segmental glomerulosclerosis; minimal change disease; podocytes