
Current lab members:
- Barbara Seitz-Polski, Professor in Immunology, PU-PH, MD PhD, UniCa
- 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
- 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.
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).
Current Projects
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Covimmune 2 study
Duration: 2020 – ongoing Funding agency: CD06 In response to the unprecedented global pandemic, our team has launched an in-depth study to analyze the immune profile of the general population
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PMMN study
Duration: 2020 – 2025 Funding agency: National Clinical Research Program (PHRC 2017) Personalized Medicine in Membranous Nephropathy: Epitope spreading in MN patients, consisting of the appearance of autoantibodies directed against
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IHMN study
Duration: 2018 – ongoing Funding agency: CD06, GIRCI Méditerranée Immunopathological Analysis of a French cohort of Membranous Nephropathy: Identifying the environmental factors associated with the disease will enable us to
Top Publications
- par Vesna BrglezBACKGROUND: Membranous nephropathy is a renal autoimmune disease associated with autoantibodies against phospholipase A2 receptor (PLA2R1) in 50-80% of cases. Patients develop immunity towards a single or multiple PLA2R1 domains, defining a cascade immunization or epitope spreading associated with worse prognosis and low rate of spontaneous remission. We aimed to compare the efficacy of standard versus personalized treatment (based on biomarker: epitope spreading) with the immunosuppressor…
- par Maxime TeisseyreRituximab, a chimeric monoclonal antibody targeting the CD20, is a key therapy for treating haematological malignancies and numerous autoimmune diseases. However, its use may be complicated by the occurrence of anti-drug antibodies (ADA), which reflect its immunogenicity. This immunogenicity varies depending on the clinical context: it remains rare in oncology, but is more common in autoimmune diseases. These ADAs may be neutralising or non-neutralising and may influence pharmacokinetics, B-cell…
- par Maxime TeisseyreNo abstract
- par Marion CremoniCONCLUSION: 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.
- par Maxime Teisseyre[This corrects the article DOI: 10.1016/j.ekir.2021.01.022.].
- par Lou C DuretCollapsing 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…
- par Alexandre DestereCONCLUSION: This algorithm could allow for early intensification of rituximab regimen in patients at high estimated risk of underdosing to increase the likelihood of remission.
- par Daisy GraçaCOVID-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…
- par Maxime TeisseyreNo abstract
- par Maxime TeisseyreNo abstract
- par Marion CremoniCONCLUSIONS: 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.
- par Jonathan AlloucheBACKGROUND: 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.
- par Barbara Seitz-PolskiNo abstract
- par Maxime TeisseyrePrimary 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…
- par Margo MontandonHomeostatic 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…
- par Maxime TeisseyrePrimary 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…
- par Alexandre GérardCONCLUSIONS: 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.
- par Maxime TeisseyreNo abstract
- par Caroline RuetschCoronavirus 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…
- par Marion CremoniFrontline 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…
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