Serum Levels of BAFF and APRIL Predict Clinical Response in Anti-PLA2R-Positive Primary Membranous Nephropathy
Primary membranous nephropathy (PMN) is a renal-specific autoimmune disease caused by circulating autoantibodies that target glomerular podocyte antigens (PLA2R/THSD7A). However, very little is known on the molecular mechanisms controlling B cell response in this nephropathy. The present study was a...
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Wiley
2019-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2019/8483650 |
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| author | Giuseppe Stefano Netti Barbara Infante Federica Spadaccino Giulia Godeas Maria Grazia Corallo Concetta Prisciandaro Laura Croce Mario Rotondi Loreto Gesualdo Giovanni Stallone Giuseppe Grandaliano Elena Ranieri |
| author_facet | Giuseppe Stefano Netti Barbara Infante Federica Spadaccino Giulia Godeas Maria Grazia Corallo Concetta Prisciandaro Laura Croce Mario Rotondi Loreto Gesualdo Giovanni Stallone Giuseppe Grandaliano Elena Ranieri |
| author_sort | Giuseppe Stefano Netti |
| collection | DOAJ |
| description | Primary membranous nephropathy (PMN) is a renal-specific autoimmune disease caused by circulating autoantibodies that target glomerular podocyte antigens (PLA2R/THSD7A). However, very little is known on the molecular mechanisms controlling B cell response in this nephropathy. The present study was aimed at correlating the serum levels of B cell activators BAFF/BLyS and APRIL with the presence of anti-PLA2R antibodies in PMN patients and with long-term clinical outcome. To this aim, 51 patients with anti-PLA2R-positive biopsy-proven PMN and nephrotic range proteinuria (>3.5 g/24 hours) were enrolled between January 2009 and December 2015 and treated with conventional 6-month immunosuppressive therapy. After 6 months, 29 patients (56.9%) cleared circulating anti-PLA2R, while in remaining 22 (43.1%), they persisted. Intriguingly, in the first group, baseline serum levels of BAFF/BLyS and APRIL were significantly lower than those in the second one. Moreover, after 6 months of immunosuppressive therapy, an overall reduction in both cytokine serum levels was observed. However, in PMN patients with anti-PLA2R clearance, this reduction was more prominent, as compared with those with anti-PLA2R persistence. When related to clinical outcome, lower baseline BAFF/BLyS (<6.05 ng/mL) and APRIL (<4.20 ng/mL) serum levels were associated with significantly higher probability to achieve complete or partial remission after 24-month follow-up. After dividing the entire study cohort into three groups depending on both cytokine baseline serum levels, patients with both BAFF/BLyS and APRIL below the cut-off showed a significantly higher rate of complete or partial remission as compared with patients with only one cytokine above the cut-off, while the composite endpoint was achieved in a very low rate of patients with both cytokines above the cut-off. Taken together, these results provide new insights into the role of BAFF/BLyS and APRIL in both the pathogenesis of anti-PLA2R-positive PMN and the response to immunosuppressive therapy. |
| format | Article |
| id | doaj-art-10b6df2eb9ac4011ad30008156c618ea |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
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| series | Journal of Immunology Research |
| spelling | doaj-art-10b6df2eb9ac4011ad30008156c618ea2025-08-20T03:55:45ZengWileyJournal of Immunology Research2314-88612314-71562019-01-01201910.1155/2019/84836508483650Serum Levels of BAFF and APRIL Predict Clinical Response in Anti-PLA2R-Positive Primary Membranous NephropathyGiuseppe Stefano Netti0Barbara Infante1Federica Spadaccino2Giulia Godeas3Maria Grazia Corallo4Concetta Prisciandaro5Laura Croce6Mario Rotondi7Loreto Gesualdo8Giovanni Stallone9Giuseppe Grandaliano10Elena Ranieri11Clinical Pathology Unit and Center for Molecular Medicine, Department of Medical and Surgical Sciences, University of Foggia, Foggia, ItalyNephrology Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, ItalyClinical Pathology Unit and Center for Molecular Medicine, Department of Medical and Surgical Sciences, University of Foggia, Foggia, ItalyNephrology Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, ItalyNephrology Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, ItalyNephrology Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, ItalyInternal Medicine and Endocrinology Unit, Laboratory for Endocrine Disruptors, ICS Maugeri I.R.C.C.S., University of Pavia, Pavia, ItalyInternal Medicine and Endocrinology Unit, Laboratory for Endocrine Disruptors, ICS Maugeri I.R.C.C.S., University of Pavia, Pavia, ItalyNephrology Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari “Aldo Moro”, Bari, ItalyNephrology Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, ItalyNephrology Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, ItalyClinical Pathology Unit and Center for Molecular Medicine, Department of Medical and Surgical Sciences, University of Foggia, Foggia, ItalyPrimary membranous nephropathy (PMN) is a renal-specific autoimmune disease caused by circulating autoantibodies that target glomerular podocyte antigens (PLA2R/THSD7A). However, very little is known on the molecular mechanisms controlling B cell response in this nephropathy. The present study was aimed at correlating the serum levels of B cell activators BAFF/BLyS and APRIL with the presence of anti-PLA2R antibodies in PMN patients and with long-term clinical outcome. To this aim, 51 patients with anti-PLA2R-positive biopsy-proven PMN and nephrotic range proteinuria (>3.5 g/24 hours) were enrolled between January 2009 and December 2015 and treated with conventional 6-month immunosuppressive therapy. After 6 months, 29 patients (56.9%) cleared circulating anti-PLA2R, while in remaining 22 (43.1%), they persisted. Intriguingly, in the first group, baseline serum levels of BAFF/BLyS and APRIL were significantly lower than those in the second one. Moreover, after 6 months of immunosuppressive therapy, an overall reduction in both cytokine serum levels was observed. However, in PMN patients with anti-PLA2R clearance, this reduction was more prominent, as compared with those with anti-PLA2R persistence. When related to clinical outcome, lower baseline BAFF/BLyS (<6.05 ng/mL) and APRIL (<4.20 ng/mL) serum levels were associated with significantly higher probability to achieve complete or partial remission after 24-month follow-up. After dividing the entire study cohort into three groups depending on both cytokine baseline serum levels, patients with both BAFF/BLyS and APRIL below the cut-off showed a significantly higher rate of complete or partial remission as compared with patients with only one cytokine above the cut-off, while the composite endpoint was achieved in a very low rate of patients with both cytokines above the cut-off. Taken together, these results provide new insights into the role of BAFF/BLyS and APRIL in both the pathogenesis of anti-PLA2R-positive PMN and the response to immunosuppressive therapy.http://dx.doi.org/10.1155/2019/8483650 |
| spellingShingle | Giuseppe Stefano Netti Barbara Infante Federica Spadaccino Giulia Godeas Maria Grazia Corallo Concetta Prisciandaro Laura Croce Mario Rotondi Loreto Gesualdo Giovanni Stallone Giuseppe Grandaliano Elena Ranieri Serum Levels of BAFF and APRIL Predict Clinical Response in Anti-PLA2R-Positive Primary Membranous Nephropathy Journal of Immunology Research |
| title | Serum Levels of BAFF and APRIL Predict Clinical Response in Anti-PLA2R-Positive Primary Membranous Nephropathy |
| title_full | Serum Levels of BAFF and APRIL Predict Clinical Response in Anti-PLA2R-Positive Primary Membranous Nephropathy |
| title_fullStr | Serum Levels of BAFF and APRIL Predict Clinical Response in Anti-PLA2R-Positive Primary Membranous Nephropathy |
| title_full_unstemmed | Serum Levels of BAFF and APRIL Predict Clinical Response in Anti-PLA2R-Positive Primary Membranous Nephropathy |
| title_short | Serum Levels of BAFF and APRIL Predict Clinical Response in Anti-PLA2R-Positive Primary Membranous Nephropathy |
| title_sort | serum levels of baff and april predict clinical response in anti pla2r positive primary membranous nephropathy |
| url | http://dx.doi.org/10.1155/2019/8483650 |
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