Membranous Nephropathy
Conditions
Keywords
Membranous nephropathy, B cells, Anti-PLA2R, Anti-CD20 antibodies
Brief summary
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_TESTIn vitro assays.
Biochemical and flow-cytometry analysis of specimen collected.
Sponsors
Mario Negri Institute for Pharmacological Research
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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. | 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. | 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. | 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. | 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. | Changes from baseline and 3,6,9,12 and 24 month. |
Countries
Italy
Contacts
CONTACTManuel Podestà, MD
Outcome results
None listed