Autoreactive B Cells in Membranous Nephropathy
ConditionMembranous Nephropathy
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorMario Negri Institute for Pharmacological Research
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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;
Disqualifiers
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.
Trial population
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 and healthy volunteers as controls
Trial design
Design model
Cohort
Time perspective
Other
Treatments tested in this trial
In vitro assays.
Diagnostic testBiochemical and flow-cytometry analysis of specimen collected.
Treatment groups
86 Participants
are divided into 3 treatment groupsGroup A: Prospective cohort1 intervention
Group B: Retrospective cohort1 intervention
Group C: Healthy volunteers cohort1 intervention
Trial outcomes
Primary outcomes
1
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.2
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.3
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.4
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.Sponsors and contacts
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Source ClinicalTrials.gov