Clinical trial NCT06988072: Study of Anti-BKPyV Immune Responses in Kidney Transplant Patients With BKPyV Viremia
Official title: Official Title Étude Des réponses Immunes Anti-BKPyV Chez Les Patients transplantés rénaux Avec BKPyV virémie
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: BK Polyomavirus
Kidney Transplant
Keywords: Polyomavirus hominis 1
Natural killer cells
T-lymphocytes
Neutralizing antibodies
Adaptative immunity
Immunologic memory
Innate immunity recognition
Trained immunity
Immune repertoire
Biomarkers
BKPyV-association nephropathy
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2025-05-23
Enrollment: 75
Sex: ALL
Minimum age (years): 7
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Study population: kidney transplant recipients with de novo BKPyV DNAemia within the first 12 months post-transplantation, including adult and pediatric patients.

Control subjects: control subjects will be matched to the study patients (criteria below with a ratio of 1-1-1):

* Healthy adult donors from the National blood bak (Etablissement Français du Sang - EFS): these control patients will be matched to study population patients on age (± 5ans) and sex
* Kidney transplant recipients without BKPyV DNAemia, enrolled within the active cohorts of the participating centers: these control patients will be matched to study population patients on age (± 5ans), enrolling center, time since transplantation (± 3 months), and sex.

Brief summary: The human pathogen BK polyomavirus (BKPyV) is a ubiquitous, small, non-enveloped DNA virus that infects over 90% of people, typically in childhood with mild or no symptoms. Following primary infection, BKPyV establishes latency predominantly in the reno-urinary tract, and can occasionally be detected in the urine without any concomitant clinical symptoms. However, among kidney transplant recipients (KTR), due to impaired cellular and humoral immunity, uncontrolled viral replication in renal tubular epithelial cells (RPTE) can occur, leading to high-level BKPyV DNAemia and significant damage to the reno-urinary system (ie polyomavirus-associated nephropathy). In the absence of any effective antiviral drug, the mainstay of therapy for significant BKPyV replication among KTR is reducing immunosuppressive drugs, despite the subsequent of risk of graft rejection. Current efforts to identify new monitoring and therapeutical strategies need to be supported by a better understanding of the dynamics of BKPyV-specific immune responses following transplantation.

Although adaptive cellular and humoral immune responses play a crucial role in the control of BKPyV reactivation among healthy individuals, immunosuppression and transplantation disrupt immune homeostasis and reshape the immune response landscape both in terms of function and fitness to new stimuli. Consequently, pre-transplant prediction of patients who will be able to control post-transplant BKPyV reactivation or who will develop BKPyV-related complications remains challenging. This knowledge gap stems from insufficient studies on the comprehensive analysis of immune responses during BKPyV reactivation. In particular, most studies to date have not investigated the role of NK cells in this context, despite their potent antiviral activity, heterogenous repertoire in each patient and their recently uncovered adaptive properties.

The hypothesis is that among KTR with de novo BKPyV DNAemia, the comprehensive analysis of anti-BKPyV immune responses (including both the description of NK cell repertoire and adaptive immune), could allow

* A better stratification of KTR at-risk for BKPyV-related complications using accessible immune biomarkers.
* The identification of the most efficient strategies of immunosuppression management for the control of BKPyV DNAemia, that could be further evaluated in a prospective cohort.
* The identification of immunological correlates for the control of BKPyV DNAemia, which aim at providing a foundation for the development of future immunotherapeutic strategies.


Eligibility criteria: Inclusion Criteria:

* No objection to participation in the research study (from patients or legal guardians)
* Affiliated to the French national social security system
* Age ≥ 7 years old
* Weight ≥ 12 kg

Additional criteria for kidney transplant recipients with BKPyV DNAemia:

* Patients who underwent kidney transplantation within 12 months prior to inclusion, regardless of the initial indication
* Detectable de novo BKPyV DNAemia within the first 12 months post-transplantation

Additional criteria for kidney transplant recipients without BKPyV DNAemia:

* Patients who underwent kidney transplantation within 12 months prior to inclusion, regardless of the initial indication
* No detectable de novo BKPyV DNAemia within the first 12 months post-transplantation

Additional criteria for healthy donors (controls):

* Age ≥ 18 years old
* Blood donation to the EFS
* Consent for the use of their blood donation for research purposes.

Exclusion Criteria:

* Objection to participation in the research study

Primary outcomes:
measure: Number of circulating NK cells
timeFrame: At inclusion
measure: Number of circulating NK cells
timeFrame: At 1 month
measure: Number of circulating NK cells
timeFrame: At 3 months
measure: Number of circulating NK cells
timeFrame: At 12 months
Secondary outcomes:
measure: Frequency of Functional Impact of BKPyV Reactivation on NK Cell Effector Functions
timeFrame: Up to 12 months
measure: Frequency of T- and B-cell specific functional responses in patients with de novo BKPyV reactivation
timeFrame: Up to 12 months
measure: Correlation between the main changes in immunosuppressive treatment and the anti-BPyV immune response
timeFrame: Up to 12 months
measure: Correlation between the main changes in immunosuppressive treatment and the control of BKPyV viremia
timeFrame: Up to 12 months
measure: Correlation between the main changes in immunosuppressive treatment and the occurrence of BKPyV nephropathy
timeFrame: Up to 12 months
measure: Correlation between the main changes in immunosuppressive treatment and the occurrence of rejection
timeFrame: Up to 12 months
measure: BKPyV viral diversity evolution during clinical course of infection
timeFrame: Up to 12 months
measure: Impact of BKPyV reactivation on alloreactive properties of NK cells
timeFrame: Up to 12 months
Other outcomes:
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