Study of Anti-BKPyV Immune Responses in Kidney Transplant Patients With BKPyV Viremia

NCT06988072 | Not Yet Recruiting

• 1 other identifier: APHP241147
• Study Type: observational
• Target: 75
• Locations: 0 countries
• Sites: N/A

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.

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

Outcome Measures

Primary Outcomes (4)

• Number of circulating NK cells

  NK cells circulating repertoire defects associated with BKPyV-DNAemia Extensive characterization of the phenotype of circulating NK cells among kidney transplant recipients with de novo BKPyV DNAemia to predict the clinically relevant outcome "BKPyV reactivation control"

  At inclusion

• Number of circulating NK cells

  NK cells circulating repertoire defects associated with BKPyV-DNAemia Extensive characterization of the phenotype of circulating NK cells among kidney transplant recipients with de novo BKPyV DNAemia to predict the clinically relevant outcome "BKPyV reactivation control"

  At 1 month

• Number of circulating NK cells

  NK cells circulating repertoire defects associated with BKPyV-DNAemia Extensive characterization of the phenotype of circulating NK cells among kidney transplant recipients with de novo BKPyV DNAemia to predict the clinically relevant outcome "BKPyV reactivation control"

  At 3 months

• Number of circulating NK cells

  NK cells circulating repertoire defects associated with BKPyV-DNAemia Extensive characterization of the phenotype of circulating NK cells among kidney transplant recipients with de novo BKPyV DNAemia to predict the clinically relevant outcome "BKPyV reactivation control"

  At 12 months

Secondary Outcomes (8)

• Frequency of Functional Impact of BKPyV Reactivation on NK Cell Effector Functions

  Up to 12 months

• Frequency of T- and B-cell specific functional responses in patients with de novo BKPyV reactivation

  Up to 12 months

• Correlation between the main changes in immunosuppressive treatment and the anti-BPyV immune response

  Up to 12 months

• Correlation between the main changes in immunosuppressive treatment and the control of BKPyV viremia

  Up to 12 months

• Correlation between the main changes in immunosuppressive treatment and the occurrence of BKPyV nephropathy

  Up to 12 months

Study Arms (3)

Kidney transplant recipients with de novo BKPyV DNAemia

kidney transplant recipients with de novo BKPyV DNAemia within the first 12 months post-transplantation, including adult and pediatric patients

Other: blood sampling

Control subjects : Healthy adult donors from the National blood bak

Other: blood sampling

Control subjects : Kidney transplant recipients without BKPyV DNAemia

Other: blood sampling

Interventions

blood sampling OTHER

At BKPyV reactivation, at 1 month, 3 months and 12 months

Kidney transplant recipients with de novo BKPyV DNAemia

Eligibility Criteria

• Age: 7 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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:
• Detectable de novo BKPyV DNAemia within the first 12 months post-transplantation
• Additional criteria for kidney transplant recipients without BKPyV DNAemia:
• 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.

You may not qualify if:

• Objection to participation in the research study

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Biospecimen

Retention: SAMPLES WITH DNA

blood samples

MeSH Terms

Interventions

Blood Specimen Collection

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Central Study Contacts

Julien Gras, MD

CONTACT

+33142494991; julien.gras@aphp.fr

Jérôme Lambert, MD PhD

CONTACT

+33142499742; jerome.lambert@u-paris.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2025
• First Posted: May 23, 2025
• Study Start: May 30, 2025
• Primary Completion (Estimated): May 30, 2028
• Study Completion (Estimated): May 30, 2028
• Last Updated: May 23, 2025

Record last verified: 2025-05