Kidney TransplantALLO-BMEMNCT07011238
Alloreactive Memory B Lymphocytes and Anti-HLA Sensitization
An observational study of Kidney Transplant, run by University Hospital, Rouen at 1 site in France.
Trial summary
In transplantation, B lymphocytes are major cellular players in the alloreactive humoral response through the production of antibodies targeting allogeneic HLA molecules expressed by the transplant. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kidney Transplant
- What is being tested?
- Patients meeting HLA immunization criteria
- Type of treatment
- Vaccines
- How many people
- 51 participants
- Where
- 1 siteFrance
- Study dates
- 17 Apr 2023to 17 Jun 2028
- How long will I take part?
- 1 Day
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients awaiting kidney transplantation and carrying HLA antibodies following immunizing events
Who may be able to join
- Age ≥ 18 years
- Rouen University Hospital patient monitored in the Nephrology and Kidney Transplantation Department, registered on the national kidney transplant waiting list
- Carrier of HLA antibodies, including at least anti-HLA2, identified during the last screening
- Notion of classic immune-promoting events including at least one previous transplant or pregnancy, or absence of a known immune-promoting event (naïve patient group)
- Incompatible graft rate (IGR)
- IGR ≥ 85% (hyperimmunized patient group with anti-HLA polyreactivity) or
Show all 10Show fewer
- IGR between 50% and 85% (immunized patient group with a more restricted repertoire of HLA reactivities) or
- IGR < 50% (naïve patient group with no known history of immune-promoting events)
- Person who has read and understood the information letter and does not object Not participating in the study
- Affiliation to a social security scheme
Who cannot join
- Patients who have received rituximab in the previous year (B-cell depleting therapy)
- Patients undergoing an HLA desensitization protocol using plasmapheresis and/or rituximab
- Patients with an active infection
- Persons deprived of their liberty by an administrative or judicial decision or persons placed under judicial protection/guardianship or curatorship
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
University Hopsital of Rouen
Rouen, 76031
Dominique DB BERTRAND, Doctor, 02 32 88 54 52 ext. +33, dominique.bertrand@chu-rouen.fr
About this study
Official title: Alloreactive Memory B Lymphocytes and Anti-HLA Sensitization in Kidney Transplantation
In transplantation, B lymphocytes are major cellular players in the alloreactive humoral response through the production of antibodies targeting allogeneic HLA molecules expressed by the transplant. In subjects sensitized to HLA antigens, the contribution of pre-existing alloreactive memory B lymphocytes (Bmem) to allograft rejection phenomena after transplantation is now recognized. It has been proposed that the identification of these Bmem during the pre-transplant period could contribute to a better assessment of post-transplant immunological risk, allowing optimization of strategies to prevent humoral rejection. However, knowledge regarding the phenotypic and functional heterogeneity of Bmem as well as their clonal diversity is still extremely limited, not allowing discrimination between pathogenic and non-pathogenic alloreactive humoral responses. Such discrimination requires a better understanding of the modalities of differentiation of alloreactive B lymphocyte responses. To this end, this study aims to characterize the clonal, phenotypic and functional properties of alloreactive Bmem in subjects awaiting renal transplantation and sensitized to HLA antigens.
Read the detailed description
The hypothesis underlying this study is that analysis of the heterogeneity of alloreactive memory B cells (Bmem) in patients carrying HLA antibodies under different levels of HLA immunization intensity, corresponding to varying degrees of exposure to HLA alloantigens, may provide insights into the mechanisms governing the formation of the overall alloreactive B-cell repertoire.
Two categories of patients sensitized to HLA antigens following immunizing events (at least one transplantation or pregnancy) and awaiting kidney transplantation will be specifically investigated:
Hyperimmunized patients, defined by an incompatible graft rate (IGR) ≥ 85%, carrying a broad HLA antibody repertoire.
Immunized patients with an IGR between 50% and 85%, carrying a more restricted HLA antibody repertoire.
These two groups represent distinct levels of exposure to HLA alloantigens. Patients exposed exclusively to immunizing events other than transplantation or pregnancy will not be included because of the absence of detectable alloreactive Bmem in such settings.
A control group will also be included, consisting of "naïve" patients carrying HLA antibodies in the absence of classical immunizing events and lacking detectable alloreactive Bmem.
Characterization of alloreactive Bmem within these groups aims to identify potential differences in clonality, phenotype, and functionality, thereby clarifying several aspects of the alloreactive humoral response.
The anticipated impact of this pilot translational study in kidney transplantation is threefold:
Acquisition of fundamental knowledge regarding the biology of human alloantigen-specific memory B cells.
Generation of preliminary data supporting subsequent investigations of alloreactive B-cell responses during acute or chronic antibody-mediated rejection.
Identification of phenotypic, clonotypic, or functional markers that may improve discrimination of the immunological risk associated with the presence of HLA antibodies and HLA-reactive B cells.
The low frequency of alloreactive Bmem, estimated at 20-150 cells per million B lymphocytes for a given HLA specificity, together with the number and epitope diversity of targeted HLA antigens, complicates direct assessment of repertoire composition and functional properties. High-throughput single-cell approaches, including RNA sequencing (RNA-seq), have become essential tools for characterizing the heterogeneity of rare cellular populations and now enable simultaneous interrogation of immune-cell repertoires and transcriptomes.
The present project will leverage these recent methodologies to directly and simultaneously investigate clonality (B-cell receptor repertoire), membrane-marker phenotype, and transcriptomic profiles of alloreactive Bmem directed against a restricted panel of HLA alleles selected according to the HLA antibody reactivity profiles of the analyzed patients. This approach enables acquisition of single-cell characteristics from several hundred alloreactive B lymphocytes per patient and comparison with polyclonal memory B-cell populations derived from patients or control subjects.
The study is designed as a pilot investigation intended to generate preliminary data before implementation of larger-scale studies involving greater numbers of patients and analyses conducted before and after transplantation.
- Conditions
- Kidney Transplant
- Being tested
- Patients meeting HLA immunization criteria
- Keywords
- B lymphocytes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Patients meeting HLA immunization criteriaDiagnostic test
At enrollment visit, a single sample of a volume of 50 ml of blood will be taken as part of routine care in order to directly and simultaneously explore the clonality (BCR repertoire), the phenotype of membrane markers and the transcriptome of Bmem alloreactive with respect to a restricted panel of HLA alleles chosen according to the HLA antibody reactivity profile of the patients analyzed
What is being measured
The primary outcome is the main question the study is designed to answer.
Level of heterogeneity of alloreactive Bmem targeting HLA alloantigens
The main objective is to determine the level of heterogeneity of alloreactive Bmem targeting HLA alloantigens of given specificities (primarily HLA-A2) in patients awaiting kidney transplantation and carrying HLA antibodies following immunizing events by evaluating the number of alloreactive Bmem clusters identified (in all patients) on the basis of their gene expression profiles (bioinformatics analysis of expression data with the open source Seurat suite
Measured: At enrollment visit
Secondary outcomes (5)
Evaluation of the level of phenotypic heterogeneity of alloreactive Bmem
To compare the level of phenotypic heterogeneity of alloreactive Bmem of given specificities (including HLA-A2) according to the immunization profile (hyperimmunization versus more restricted immunization) by evaluating the number of alloreactive Bmem clusters identified (in all patients) on the basis of their gene expression profiles (bioinformatics analysis of expression data with the open source Seurat suite
Measured: At enrollment visit
Evaluation of the level of transcriptional heterogeneity of alloreactive Bmem
To compare the level of transcriptional heterogeneity of alloreactive Bmem of given specificities (including HLA-A2) according to the immunization profile (hyperimmunization versus more restricted immunization) by evaluating the number of alloreactive Bmem clusters identified (in all patients) on the basis of their gene expression profiles (bioinformatics analysis of expression data with the open source Seurat suite
Measured: At enrollment visit
Clonality of Bmem specific to each HLA antigen tested
Evaluation of VDJ junction sequences of IgH genes coding for the BCR of alloreactive Bmem, analyzed with the IgBlast tool
Measured: At enrollment visit
Somatic mutations of the BCR of Bmem IgG+ or IgM+
Determine the number of somatic mutations of the BCR of Bmem IgG+ or IgM+ in each patient, and according to the IgBlast immunization profile (calculation of the average number of somatic mutations of the VDJ junction of the IgH genes)
Measured: At enrollment visit
Ratio of the number of Bmem IgM+/IgG+
Determination of the Bmem IgM+/IgG+ ratio in each patient based on the immunization profile
Measured: At enrollment visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2025
- Study start17 Apr 2023
- Primary completion17 Jun 2028 (estimated)
- Study completion17 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kidney TransplantStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 51 participants (estimated)
- Target duration
- 1 Day
Sponsor and investigators
- Lead sponsor
- University Hospital, Rouen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07011238
- Sponsor's protocol ID
- 2021/301/OB
- Other IDs
- 2021-A02507-34
- Acronym
- ALLO-BMEM
- Status last verified
- Feb 2026
- First submitted
- 30 May 2025
- Last updated
- 22 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The data provided will be the property of the sponsor and will be used solely for its own research activities.
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Alloreactive Memory B Lymphocytes and Anti-HLA Sensitization in Kidney Transplantation
- ClinicalTrials.gov ID
- NCT07011238
- Acronym / sponsor ID
- ALLO-BMEM / 2021/301/OB
- Conditions
- Kidney Transplant
- Keywords
- B lymphocytes
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 51 participants (estimated)
- Lead sponsor
- University Hospital, RouenUniversity, hospital or other
- Study start
- 17 Apr 2023 (actual)
- Primary completion
- 17 Jun 2028 (estimated)
- Study completion
- 17 Jun 2028 (estimated)
- First posted
- 8 Jun 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In transplantation, B lymphocytes are major cellular players in the alloreactive humoral response through the production of antibodies targeting allogeneic HLA molecules expressed by the transplant. In subjects sensitized to HLA antigens, the contribution of pre-existing alloreactive memory B lymphocytes (Bmem) to allograft rejection phenomena after transplantation is now recognized. It has been proposed that the identification of these Bmem during the pre-transplant period could contribute to a better assessment of post-transplant immunological risk, allowing optimization of strategies to prevent humoral rejection. However, knowledge regarding the phenotypic and functional heterogeneity of Bmem as well as their clonal diversity is still extremely limited, not allowing discrimination between pathogenic and non-pathogenic alloreactive humoral responses. Such discrimination requires a better understanding of the modalities of differentiation of alloreactive B lymphocyte responses. To this end, this study aims to characterize the clonal, phenotypic and functional properties of alloreactive Bmem in subjects awaiting renal transplantation and sensitized to HLA antigens.
Detailed description
The hypothesis underlying this study is that analysis of the heterogeneity of alloreactive memory B cells (Bmem) in patients carrying HLA antibodies under different levels of HLA immunization intensity, corresponding to varying degrees of exposure to HLA alloantigens, may provide insights into the mechanisms governing the formation of the overall alloreactive B-cell repertoire.
Two categories of patients sensitized to HLA antigens following immunizing events (at least one transplantation or pregnancy) and awaiting kidney transplantation will be specifically investigated:
Hyperimmunized patients, defined by an incompatible graft rate (IGR) ≥ 85%, carrying a broad HLA antibody repertoire.
Immunized patients with an IGR between 50% and 85%, carrying a more restricted HLA antibody repertoire.
These two groups represent distinct levels of exposure to HLA alloantigens. Patients exposed exclusively to immunizing events other than transplantation or pregnancy will not be included because of the absence of detectable alloreactive Bmem in such settings.
A control group will also be included, consisting of "naïve" patients carrying HLA antibodies in the absence of classical immunizing events and lacking detectable alloreactive Bmem.
Characterization of alloreactive Bmem within these groups aims to identify potential differences in clonality, phenotype, and functionality, thereby clarifying several aspects of the alloreactive humoral response.
The anticipated impact of this pilot translational study in kidney transplantation is threefold:
Acquisition of fundamental knowledge regarding the biology of human alloantigen-specific memory B cells.
Generation of preliminary data supporting subsequent investigations of alloreactive B-cell responses during acute or chronic antibody-mediated rejection.
Identification of phenotypic, clonotypic, or functional markers that may improve discrimination of the immunological risk associated with the presence of HLA antibodies and HLA-reactive B cells.
The low frequency of alloreactive Bmem, estimated at 20-150 cells per million B lymphocytes for a given HLA specificity, together with the number and epitope diversity of targeted HLA antigens, complicates direct assessment of repertoire composition and functional properties. High-throughput single-cell approaches, including RNA sequencing (RNA-seq), have become essential tools for characterizing the heterogeneity of rare cellular populations and now enable simultaneous interrogation of immune-cell repertoires and transcriptomes.
The present project will leverage these recent methodologies to directly and simultaneously investigate clonality (B-cell receptor repertoire), membrane-marker phenotype, and transcriptomic profiles of alloreactive Bmem directed against a restricted panel of HLA alleles selected according to the HLA antibody reactivity profiles of the analyzed patients. This approach enables acquisition of single-cell characteristics from several hundred alloreactive B lymphocytes per patient and comparison with polyclonal memory B-cell populations derived from patients or control subjects.
The study is designed as a pilot investigation intended to generate preliminary data before implementation of larger-scale studies involving greater numbers of patients and analyses conducted before and after transplantation.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Target follow-up
- 1 Day
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients awaiting kidney transplantation and carrying HLA antibodies following immunizing events
Key inclusion criteria (10 listed)
- Age ≥ 18 years
- Rouen University Hospital patient monitored in the Nephrology and Kidney Transplantation Department, registered on the national kidney transplant waiting list
- Carrier of HLA antibodies, including at least anti-HLA2, identified during the last screening
- Notion of classic immune-promoting events including at least one previous transplant or pregnancy, or absence of a known immune-promoting event (naïve patient group)
- Incompatible graft rate (IGR)
Key exclusion criteria (4 listed)
- Patients who have received rituximab in the previous year (B-cell depleting therapy)
- Patients undergoing an HLA desensitization protocol using plasmapheresis and/or rituximab
- Patients with an active infection
- Persons deprived of their liberty by an administrative or judicial decision or persons placed under judicial protection/guardianship or curatorship
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Patients meeting HLA immunization criteriaAt enrollment visit, a single sample of a volume of 50 ml of blood will be taken as part of routine care in order to directly and simultaneously explore the clonality (BCR repertoire), the phenotype of membrane markers and the transcriptome of Bmem alloreactive with respect to a restricted panel of HLA alleles chosen according to the HLA antibody reactivity profile of the patients analyzed | Diagnostic test | – |
Primary outcome
Level of heterogeneity of alloreactive Bmem targeting HLA alloantigens
Time frame: At enrollment visit
The main objective is to determine the level of heterogeneity of alloreactive Bmem targeting HLA alloantigens of given specificities (primarily HLA-A2) in patients awaiting kidney transplantation and carrying HLA antibodies following immunizing events by evaluating the number of alloreactive Bmem clusters identified (in all patients) on the basis of their gene expression profiles (bioinformatics analysis of expression data with the open source Seurat suite
5 secondary outcomes
Evaluation of the level of phenotypic heterogeneity of alloreactive Bmem
Time frame: At enrollment visit
Evaluation of the level of transcriptional heterogeneity of alloreactive Bmem
Time frame: At enrollment visit
Clonality of Bmem specific to each HLA antigen tested
Time frame: At enrollment visit
Somatic mutations of the BCR of Bmem IgG+ or IgM+
Time frame: At enrollment visit
Ratio of the number of Bmem IgM+/IgG+
Time frame: At enrollment visit
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2026.
- Individual participant dataSharing planned: Yes. The data provided will be the property of the sponsor and will be used solely for its own research activities.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Kidney Transplant, run by University Hospital, Rouen at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact David DM MALLET, Director (02 32 88 82 65 ext. +33, David.Mallet@chu-rouen.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Level of heterogeneity of alloreactive Bmem targeting HLA alloantigens (time frame: At enrollment visit). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2026.