Autoreactive B Cells in Membranous Nephropathy
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: In vitro assays..
- Who it may be relevant to
- Registry conditions: Membranous Nephropathy. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Italy
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
PLA2R Autoreactive B-Cell Subsets and Immune Cell Monitoring in Membranous Nephropathy: Identification of Outcome Predictors and Novel Insights Into Disease Pathogenesis
Overview
Membranous nephropathy (MN) is the most frequent cause of nephrotic syndrome (NS) in adults. The majority of MN patients show detectable circulating antibodies against the M-type phospholipase A2 receptor (PLA2R). Infusion of anti-CD20 monoclonal antibodies results in a profound depletion of B-cells, which are thought to be responsible for anti-PLA2R production. B-cell depletion is followed by NS remission in 70% of cases. Limited evidence highlighted that differences in the B- and T-cell compartments may exist between responders and non-responders. Owing to the non-homogenous efficacy of anti-CD20 treatment, investigators hypothesize that in MN patients who experience NS remission after B-cell depleting therapy, autoreactive B-cells may be mostly circulating, whereas in patients who do not respond to the same treatment, autoreactive B-cells may chiefly reside into secondary lymphoid organs - and thus be more resistant to the drug action. Researchers will therefore extensively analyze the circulating immune repertoire of MN patients before and after the infusion of B-cell lineage depleting agents, assessing the presence of circulating PLA2R autoreactive B cells from appropriately stratified responder and non-responder patients. Patients and healthy controls will be enrolled in this study. Patients will be stratified according to gender, anti-PLA2R status, type of B-cell lineage depleting agent received and response to treatment.
Interventions
- Diagnostic test In vitro assays.
Biochemical and flow-cytometry analysis of specimen collected.
Primary outcome measures
- Differences between anti-PLA2R positive MN patients and anti-PLA2R negative MN patients and healthy controls in the frequency of anti-PLA2R autoreactive circulating B-cells. [Time frame: Changes from baseline and 3,6,9,12 and 24 month.]
- Differences between anti-PLA2R positive MN patients and anti-PLA2R negative MN patients and healthy controls in the frequency of immunoglobulin- and cytokine-secreting circulating B-cell subsets in resting and stimulated conditions. [Time frame: Changes from baseline and 3,6,9,12 and 24 month.]
- Differences between anti-PLA2R positive MN patients and anti-PLA2R negative MN patients and healthy controls in spontaneous / stimulated immunoglobulin (including anti-PLA2R) and cytokine release from circulating B-cell subpopulations. [Time frame: Changes from baseline and 3,6,9,12 and 24 month.]
- Differences between MN patients and healthy controls, and between responders and non-responders in the frequency of circulating B-cell subpopulations. [Time frame: Changes from baseline and 3,6,9,12 and 24 month.]
- Differences between MN patients and healthy controls, and between responders and non-responders in the frequency of circulating T-cell, NK-cell, monocyte and dendritic cell subpopulations. [Time frame: Changes from baseline and 3,6,9,12 and 24 month.]
Eligibility criteria
Inclusion criteria
Patients inclusion criteria
- Males and females.
- Adults (> 18 years old).
- Patients with biopsy-proven idiopathic MN, who are candidate to receive (prospective cohort) or who already received (retrospective cohort) a B-cell depleting treatment as per center clinical practice.
- Mental state is such that they are able to understand and give valid consent to the study;
- Written informed consent according to the guidelines of the Declaration of Helsinki.
Healthy volunteers inclusion criteria
- Male and female (>18 years) not known to suffer of any significant illness;
- Not assuming any medication or drug on a regular basis;
- Negative urine analysis (urine dipstick, multistick);
- Written informed consent according to the guidelines of the Declaration of Helsinki
Exclusion criteria
Patients exclusion criteria
- Reasonable possibility of a secondary cause of MN (e.g.systemic lupus erythematosus, active hepatitis B, malignancy, drugs such as gold salts and penicillamine).
- Legal incapacity, intellectual disability/mental retardation, dementia, uncooperative attitude or any other evidence that patient will not be able to understand the study procedures and aims and to give written informed consent.
Healthy volunteers exclusion criteria
\- Legal incapacity, intellectual disability/mental retardation, dementia, uncooperative attitude or any other evidence that patient will not be able to understand the study procedures and aims and to give written informed consent.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Observational model
- Cohort
Study locations
Italy · 1 center
- Centro di Ricerche Cliniche per le Malattie Rare " Aldo e Cele Daccò" — Ranica
Identifiers
NCT: NCT04095156 · PEPTIDE