Current lab members:

• Barbara Seitz-Polski, Professor in Immunology, PU-PH, MD PhD, UniCa
• Marina Shkreli, CR, INSERM
• Marion Cremoni, University Hospital Assistant, PhD student, UniCa
• Maxime Teisseyre, University Hospital Assistant, PhD student, UniCa
• Céline Fernandez, MsC, engineer, CHU de Nice
• Kévin Zorzi, MsC, engineer, CHU de Nice
• Vesna Brglez, PhD, engineer, CHU de Nice
• El Mai Mounir, PhD, engineer, CHU de Nice
• Delphine Buret, MsC, engineer, CNRS
• Elisa Allart, MsC, engineer, CNRS
• Agathe Debris-Cafort, MsC, engineer, CNRS
• Scarlette Cassal, MSc, engineer, CHU de Nice
• Erendira Vazquez-Salazar, technician, CHU de Nice

We focus on understanding and treating nephrotic syndrome in adults, particularly Membranous Nephropathy (MN) and Focal and Segmental Glomerulosclerosis (FSGS).

Under the leadership of Prof. Seitz-Polski, our research on MN explores how environmental factors like air pollution and toxic substances increase disease incidence by overactivating the Th17 immune response, and we work on optimizing rituximab therapy through personalized dosing algorithms.

Dr. Shkreli’s work on FSGS highlights the role of telomerase in kidney regeneration and disease progression, aiming to harness telomerase for repairing damaged podocytes and developing new therapeutic strategies.

Our lab is dedicated to improving lives through rigorous scientific inquiry and innovative treatments. Thank you for supporting our mission to advance kidney health.

In adults, Nephrotic syndrome are related to two main diseases: Membranous Nephropathy and Focal and Segmental Glomerulosclerosis. Our research focuses on two main areas:

Immunopathology and Immunotherapy of Membranous Nephropathy (Prof. Seitz-Polski)

Membranous Nephropathy (MN) is a rare autoimmune kidney disease, related to autoantibodies directed against podocyte antigens (PLA2R1 70% and THSD7A 3%). Membranous Nephropathy is the first cause of adult nephrotic syndrome. The disease evolution goes from chronic kidney failure to spontaneous remission, or persistent nephrotic syndrome. Prof. Seitz-Polski is head of the Rare Disease Reference for nephrotic syndrome since 2017 and developed 2 axes of research:

(i) Impact of the environment on the orientation of the immune response in MN patients

Membranous Nephropathy incidence has increased over the last 20 years and epidemiological studies highlighted an association between air pollution exposure and Membranous Nephropathy incidence. The team demonstrated that MN patients presented an imbalance in their cytokine profile in favor of the Th17 responses. Exposome analysis of MN patients demonstrated that patients living in areas with high particulate matter levels, or working in the construction sector (exposed to occupational toxic substances: asbestos, organic solvents) exhibited overactivation of the Th17 pathway. This result has been confirmed in the general population (n=314). Exposure of peripheral blood immune cells from MN patients to particulate matter induces the production of pro-inflammatory cytokines from Th17 pathway. We then developed a mouse model of MN to determine (i) whether particulate matter exposure triggers Th17-dependent tissue inflammation in mice and promote MN, (ii) how particulate matter exposure disrupts kidney podocytes (AIRGEM Project funded by ORKID and ANR AAPG 2024).

 (ii) Immunomonitoring and Immunotherapy

Rituximab, a monoclonal anti-CD20 antibody, is the first line therapy for MN patients. It targets B lymphocytes and induces a depletion of anti-PLA2R1 or anti-THSD7A antibodies achieving remission. Immunomonitoring of rituximab revealed that 40% of patients developed anti-drug antibodies, leading to resistance and relapse. Furthermore, residual rituximab dosing revealed that nephrotic patients had urinary drug loss leading to drug underdosing. In collaboration with the start-up Exactcure, the team has developed a predictive algorithm for the risk of rituximab underdosing, capable of predicting the dose of drug to administer. This algorithm will be validated in a randomized trial starting in 2024 (iRitux PHRC 2022).

Telomerase and adult stem cell homeostasis in Focal and Segmental Glomerulosclerosis (Dr. Shkreli)

Dr. Shkreli provided the first insights into the involvement of telomerase in nephrotic syndrome and regeneration and developed 2 axes of research:

(i) To promote regeneration in the adult mammalian kidney

Homeostatic renal filtration relies on the integrity of glomerular visceral cells called podocytes. These highly specialized cells are damaged in nephrotic syndrome. We found that telomerase serves critical functions in adult kidney regeneration. We indeed showed that endogenous telomerase is required for glomerular renewal following injury, and we found that a pulse of telomerase expression is sufficient to activate a progenitor cell population that clonally expend and repopulate the podocyte compartment. We are using in vivo approaches to unveil the origin of podocyte progenitor cells, and we aim to determine if and how these cells are deregulated in pathological conditions and during organismal aging.

(ii) Targeting telomerase functions in kidney disease

Analysis of telomerase overexpressing mice revealed its critical role in collapsing focal segmental glomerulosclerosis (FSGS), a proliferative kidney disease characterized by rapid progression to end-stage renal disease (ESRD). We are deciphering the molecular mechanisms targeted by telomerase and regulating its functions upon FSGS initiation and progression in order to find alternative therapeutic approaches.

Current Projects

Top Publications

• Anti Phospholipase A2 Receptor 1 Antibodies and Membranous Nephropathy Recurrence After Kidney Transplantation
  19 décembre 2024 par Marion Cremoni
  CONCLUSION: The presence of anti-PLA2R1 antibodies prior to transplantation was a strong predictor of recurrence of allograft membranous nephropathy. An individualized immunomonitoring and management strategy for kidney transplant candidates with anti-PLA2R1-associated membranous nephropathy should be considered.
• Corrigendum to "Analysis and Management of Rituximab Resistance in PLA2R1-Associated Membranous Nephropathy" [<em>Kidney International Reports</em> Volume 6, Issue 4, April 2021, Pages 1183-1188]
  31 juillet 2024 par Maxime Teisseyre
  [This corrects the article DOI: 10.1016/j.ekir.2021.01.022.].
• Targeting WIP1 phosphatase promotes partial remission in experimental collapsing glomerulopathy
  29 février 2024 par Lou C Duret
  Collapsing focal segmental glomerulosclerosis (FSGS), also known as collapsing glomerulopathy (CG), is the most aggressive variant of FSGS and is characterized by a rapid progression to kidney failure. Understanding CG pathogenesis represents a key step for the development of targeted therapies. Previous work implicated the telomerase protein component TERT in CG pathogenesis, as transgenic TERT expression in adult mice resulted in a CG resembling that seen in human primary CG and HIV-associated…
• Optimization of Rituximab Therapy in Adult Patients With PLA2R1-Associated Membranous Nephropathy With Artificial Intelligence
  5 février 2024 par Alexandre Destere
  CONCLUSION: This algorithm could allow for early intensification of rituximab regimen in patients at high estimated risk of underdosing to increase the likelihood of remission.
• Both Humoral and Cellular Immune Responses to SARS-CoV-2 Are Essential to Prevent Infection: a Prospective Study in a Working Vaccinated Population from Southern France
  22 août 2023 par Daisy Graça
  COVID-19 vaccines have significantly decreased the number of severe cases of the disease, but the virus circulation remains important, and questions about the need of new vaccination campaigns remain unanswered. The individual's protection against SARS-CoV-2 infection is most commonly measured by the level and the neutralizing capacity of antibodies produced against SARS-CoV-2. T cell response is a major contributor in viral infection, and several studies have shown that cellular T cell response…
• Risk Factors Associated with the Occurrence of Anti-rituximab Antibodies in Membranous Nephropathy
  21 mars 2023 par Maxime Teisseyre
  No abstract
• Humoral and cellular responses after a third dose of SARS-CoV-2 mRNA vaccine in patients with glomerular disease
  10 novembre 2022 par Maxime Teisseyre
  No abstract
• Toxic Occupational Exposures and Membranous Nephropathy
  25 octobre 2022 par Marion Cremoni
  CONCLUSIONS: Patients with membranous nephropathy were more frequently exposed to certain occupational toxic substances, such as asbestos and organic solvents, than the general population. This occupational exposure was more frequent in men and in patients with PLA2R1 epitope spreading.
• Air pollution exposure induces a decrease in type II interferon response: A paired cohort study
  2 octobre 2022 par Jonathan Allouche
  BACKGROUND: While air pollution is a major issue due to its harmful effects on human health, few studies focus on its impact on the immune system and vulnerability to viral infections. The lockdown declared following the COVID-19 pandemic represents a unique opportunity to study the large-scale impact of variations in air pollutants in real life. We hypothesized that variations in air pollutants modify Th1 response represented by interferon (IFN) γ production.
• Editorial: Immune dysfunction in nephrotic syndrome – recent advances and new roads ahead
  19 août 2022 par Barbara Seitz-Polski
  No abstract
• Advances in the Management of Primary Membranous Nephropathy and Rituximab-Refractory Membranous Nephropathy
  23 mai 2022 par Maxime Teisseyre
  Primary membranous nephropathy (pMN) is an auto-immune disease characterized by auto-antibodies targeting podocyte antigens resulting in activation of complement and damage to the glomerular basement membrane. pMN is the most common cause of nephrotic syndrome in adults without diabetes. Despite a very heterogeneous course of the disease, the treatment of pMN has for many years been based on uniform management of all patients regardless of the severity of the disease. The identification of…
• Telomerase is required for glomerular renewal in kidneys of adult mice
  12 février 2022 par Margo Montandon
  Homeostatic renal filtration relies on the integrity of podocytes, which function in glomerular filtration. These highly specialized cells are damaged in 90% of chronic kidney disease, representing the leading cause of end-stage renal failure. Although modest podocyte renewal has been documented in adult mice, the mechanisms regulating this process remain largely unknown and controversial. Using a mouse model of Adriamycin-induced nephropathy, we find that the recovery of filtration function…
• Rituximab Immunomonitoring Predicts Remission in Membranous Nephropathy
  1 novembre 2021 par Maxime Teisseyre
  Primary membranous nephropathy (pMN) is an autoimmune kidney disease and a common cause of nephrotic syndrome in adults. Rituximab is becoming a first line therapy for patients with persistent nephrotic syndrome with proven safety and efficacy, achieving remission in 60%-80% of cases. For the remaining 20%-40% of patients there is an urgent need to identify early biomarkers of resistance to rituximab to adapt therapeutic management. In nephrotic patients, rituximab is found in the blood more…
• Baseline and early functional immune response is associated with subsequent clinical outcomes of PD-1 inhibition therapy in metastatic melanoma patients
  5 juin 2021 par Alexandre Gérard
  CONCLUSIONS: Our findings indicate that cytokine levels after in vitro non-specific stimulation could be a promising biomarker to predict the outcome of PD-1 inhibition therapy.
• Analysis and Management of Rituximab Resistance in PLA2R1-Associated Membranous Nephropathy
  29 avril 2021 par Maxime Teisseyre
  No abstract
• Functional Exhaustion of Type I and II Interferons Production in Severe COVID-19 Patients
  15 février 2021 par Caroline Ruetsch
  Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged in Wuhan in December 2019 and has since spread across the world. Even though the majority of patients remain completely asymptomatic, some develop severe systemic complications. In this prospective study we compared the immunological profile of 101 COVID-19 patients with either mild, moderate or severe form of the disease according to the WHO classification, as well as of 50…
• Humoral and Cellular Response of Frontline Health Care Workers Infected by SARS-CoV-2 in Nice, France: A Prospective Single-Center Cohort Study
  15 février 2021 par Marion Cremoni
  Frontline health care workers (HCWs) have been particularly exposed to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) since the start of the pandemic but the clinical features and immune responses of those infected with SARS-CoV-2 have not been well described. In a prospective single center cohort study, we enrolled 196 frontline HCWs exposed to the SARS-Cov-2 and 60 patients with moderate and severe forms of the coronavirus disease 2019 (COVID-19). Serological tests and cytokines…
• Th17-Immune Response in Patients With Membranous Nephropathy Is Associated With Thrombosis and Relapses
  16 décembre 2020 par Marion Cremoni
  Membranous nephropathy (MN) is a rare autoimmune kidney disease. Most autoimmune diseases are associated with a pro-inflammatory Th17-immune response, but little is known about immune dysregulation in MN. In China, MN was associated with exposure to fine air particulate matter (PM(2.5)) that could act as a danger signal and redirect immune response toward the Th2 or Th17 pathway. We aimed to analyze the cytokine profile of MN patients and to study the possible environmental factors involved in…
• Complement Pathways in Membranous Nephropathy: Complex and Multifactorial
  15 mai 2020 par Vesna Brglez
  No abstract
• Anti-PLA2R1 Antibodies Containing Sera Induce In Vitro Cytotoxicity Mediated by Complement Activation
  22 février 2020 par Maël Lateb
  The phospholipase A2 receptor (PLA2R1) is the major autoantigen in idiopathic membranous nephropathy (MN). However, the pathogenic role of anti-PLA2R1 autoantibodies is unclear. Our aim was to evaluate the in vitro cytotoxicity of anti-PLA2R1 antibodies mediated by complement. Forty-eight patients with PLA2R1-related MN from the prospective cohort SOURIS were included. Anti-PLA2R1 titer, epitope profile, and anti-PLA2R1 IgG subclasses were characterized by ELISA. Cell cytotoxicity was evaluated…

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