Antibody-mediated RejectionCOR-HUMNCT04026087
Subclass of Donor-specific Antibody as a Risk Factor of Antibody Mediated Rejection in Renal Transplantation
An observational study of Antibody-mediated Rejection, run by University Hospital, Montpellier at 1 site in France.
Trial summary
Antibody-mediated rejection is now recognized as the first cause of long-term kidney transplant loss. This type of rejection is mediated by the presence of graft-specific antibodies, usually directed against HLA (Human Leukocyte Antigens), called DSA (Donor Specific Antibody). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Antibody-mediated Rejection
- How many people
- 100 participants
- Where
- 1 siteFrance
- Study dates
- 18 Jul 2019to 15 Feb 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
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 18 years old and over with kidney transplant and who have DSA
Who may be able to join
- - Patients over 18 years old
- Renal transplant patients followed at the University Hospital of Montpellier presenting a DSA de novo during follow-up.
- Affiliation or beneficiary of a social security scheme.
- Inclusion criteria specific to patients whose graft biopsy has already been performed
- Patients who consented to the collection of a plasma sample on graft biopsy day and use in future programs (Collection DC-2014-2328)
- Collection of non-opposition to participate in the study
Show all 10Show fewer
- Inclusion criteria specific to patients whose biopsy of the graft has not already been performed:
- Eligible for graft biopsy for humoral-mediated rejection (according to Banff 2015 classification) (Appendix 1)
- Collection of non-opposition to participate in the study
- Signature of informed consent to participate in the collection of a plasma sample on graft biopsy day and use in future programs (Collection DC-2014-2328)
Who cannot join
- Pregnant or lactating women according to Article L1121 5 of the health public Code
- Vulnerable persons according to article L1121-6 of the health public Code
- Major persons placed under guardianship or curator
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Characterization of the Subclass of Donor-specific Antibody Determined in Mass Spectrometry as a Risk Factor of Antibody Mediated Rejection in Renal Transplantation
Antibody-mediated rejection is now recognized as the first cause of long-term kidney transplant loss. This type of rejection is mediated by the presence of graft-specific antibodies, usually directed against HLA (Human Leukocyte Antigens), called DSA (Donor Specific Antibody).
De novo DSA (ie, post-transplantation) is detected in approximately 20% of transplant recipients in the first five years, and is a major risk factor for antibody mediated rejection and graft loss.
Read more
All anti-HLA antibodies therefore do not have the same pathogenicity. Some teams have shown that the detection of IgG3 anti-HLA by cytometry is associated with a higher risk of humoral rejection but these results have not been confirmed by others. One of the limitations of the cytometry by Luminex technique is that it only informs the detection of each subclass but does not allow analysis of the distribution of the different subclasses of a DSA.
A method has been developed for the relative detection and quantification of different subclasses of the DSA using the mass spectrometry technique and will be tested during this study. This new quantification method therefore opens up the prospect of studying whether, not only the presence but especially the distribution of IgG subclasses, in particular IgG3, could constitute a reliable and robust marker of humoral rejection.
Read the detailed description
Antibody-mediated rejection is now recognized as the first cause of long-term kidney transplant loss. This type of rejection is mediated by the presence of graft-specific antibodies, usually directed against HLA (Human Leukocyte Antigens), called DSA (Donor Specific Antibody). It results from the interaction between DSA and HLA present on the surface of graft endothelial cells, complement activation, endothelial cell activation and recruitment of inflammatory cells within the renal microcirculation leading to a graft dysfunction.
De novo DSA (ie, post-transplantation) is detected in approximately 20% of transplant recipients in the first five years, and is a major risk factor for antibody mediated rejection and graft loss. However, the presence of a DSA is not always associated with humoral rejection.
All anti-HLA antibodies therefore do not have the same pathogenicity. The antibody titre (assessed by the fluorescence average (MFI) on Luminex beads) is involved in the risk of rejection but is far from explaining the disparities in clinical evolution.
DSA are mainly IgG of different subclasses whose distribution could have a major impact on their pathogenicity. Indeed, complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) functions differ according to IgG subclass. IgG3 is the subclass that has the greatest potential for complement activation followed by IgG1. IgG3 and IgG1 are also the two subclasses with the best affinities for the FcγRIIIa activating receptor for ADCC mediated by Natural Killer (NK) cells.
Some teams have shown that the detection of IgG3 anti-HLA by cytometry is associated with a higher risk of humoral rejection but these results have not been confirmed by others. One of the limitations of the cytometry by Luminex technique is that it only informs the detection of each subclass but does not allow analysis of the distribution of the different subclasses of a DSA.
A method has been developed for the relative detection and quantification of different subclasses of the DSA using the mass spectrometry technique and will be tested during this study. This new quantification method therefore opens up the prospect of studying whether, not only the presence but especially the distribution of IgG subclasses, in particular IgG3, could constitute a reliable and robust marker of humoral rejection.
- Conditions
- Antibody-mediated Rejection
- Keywords
- Renal transplantation, antibody-mediated rejection, DSA, mass spectrometry technique
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| patient with kidney transplant | Blood sample will be took from subjects during this research |
What is being measured
The primary outcome is the main question the study is designed to answer.
distribution of DSA IgG subclasses
the performance of the distribution of DSA IgG subclasses for the diagnosis of humoral rejection in renal transplant patients with Donor Specific Antibodies
Measured: day 0 (inclusion visit)
Secondary outcomes (3)
histological criteria for humoral rejection
Link between the distribution of DSA IgG subclasses and histological criteria for humoral rejection (according to the Banff International Classification 2015)
Measured: day 0 (inclusion visit)
degradation of graft function
Link between the distribution of DSA IgG subclasses and degradation of graft function (glomerular filtration rate loss of more than 25%)
Measured: 1 year after inclusion of subjects
graft loss
Link between the distribution of DSA IgG subclasses and graft loss
Measured: 1 year after inclusion of subjects
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2019
- Study start18 Jul 2019
- Primary completion6 May 2022
- Study completion15 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Antibody-mediated RejectionStudies of the same condition, open and under way.
- More trials run by University Hospital, MontpellierThe sponsor's other registered studies.
- 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
- Cohort
- Time perspective
- Other
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Montpellier
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Vincent Pernin, Doctor, Principal investigator, UH Montpellier
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04026087
- Sponsor's protocol ID
- RECHMPL18_0455 UF7724
- Acronym
- COR-HUM
- Status last verified
- Feb 2023
- First submitted
- 11 Jul 2019
- Last updated
- 23 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Pernin V, Bec N, Beyze A, Bourgeois A, Szwarc I, Champion C, Chauvin A, Rene C, Mourad G, Merville P, Visentin J, Perrochia H, Couzi L, Larroque C, Le Quintrec M. IgG3 donor-specific antibodies with a proinflammatory glycosylation profile may be associated with the risk of antibody-mediated rejection after kidney transplantation. Am J Transplant. 2022 Mar;22(3):865-875. doi: 10.1111/ajt.16904. Epub 2021 Dec 18.
PubMed 34863025Pernin V, Beyze A, Szwarc I, Bec N, Salsac C, Perez-Garcia E, Mourad G, Merville P, Visentin J, Perrochia H, Larroque C, Couzi L, Le Quintrec M. Distribution of de novo Donor-Specific Antibody Subclasses Quantified by Mass Spectrometry: High IgG3 Proportion Is Associated With Antibody-Mediated Rejection Occurrence and Severity. Front Immunol. 2020 Jun 2;11:919. doi: 10.3389/fimmu.2020.00919. eCollection 2020.
PubMed 32670261
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterization of the Subclass of Donor-specific Antibody Determined in Mass Spectrometry as a Risk Factor of Antibody Mediated Rejection in Renal Transplantation
- ClinicalTrials.gov ID
- NCT04026087
- Acronym / sponsor ID
- COR-HUM / RECHMPL18_0455 UF7724
- Conditions
- Antibody-mediated Rejection
- Keywords
- Renal transplantation, antibody-mediated rejection, DSA, mass spectrometry technique
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- University Hospital, MontpellierUniversity, hospital or other
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France
- Study start
- 18 Jul 2019 (actual)
- Primary completion
- 6 May 2022 (actual)
- Study completion
- 15 Feb 2023 (actual)
- First posted
- 19 Jul 2019 (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.
Antibody-mediated rejection is now recognized as the first cause of long-term kidney transplant loss. This type of rejection is mediated by the presence of graft-specific antibodies, usually directed against HLA (Human Leukocyte Antigens), called DSA (Donor Specific Antibody).
De novo DSA (ie, post-transplantation) is detected in approximately 20% of transplant recipients in the first five years, and is a major risk factor for antibody mediated rejection and graft loss.
All anti-HLA antibodies therefore do not have the same pathogenicity. Some teams have shown that the detection of IgG3 anti-HLA by cytometry is associated with a higher risk of humoral rejection but these results have not been confirmed by others. One of the limitations of the cytometry by Luminex technique is that it only informs the detection of each subclass but does not allow analysis of the distribution of the different subclasses of a DSA.
A method has been developed for the relative detection and quantification of different subclasses of the DSA using the mass spectrometry technique and will be tested during this study. This new quantification method therefore opens up the prospect of studying whether, not only the presence but especially the distribution of IgG subclasses, in particular IgG3, could constitute a reliable and robust marker of humoral rejection.
Detailed description
Antibody-mediated rejection is now recognized as the first cause of long-term kidney transplant loss. This type of rejection is mediated by the presence of graft-specific antibodies, usually directed against HLA (Human Leukocyte Antigens), called DSA (Donor Specific Antibody). It results from the interaction between DSA and HLA present on the surface of graft endothelial cells, complement activation, endothelial cell activation and recruitment of inflammatory cells within the renal microcirculation leading to a graft dysfunction.
De novo DSA (ie, post-transplantation) is detected in approximately 20% of transplant recipients in the first five years, and is a major risk factor for antibody mediated rejection and graft loss. However, the presence of a DSA is not always associated with humoral rejection.
All anti-HLA antibodies therefore do not have the same pathogenicity. The antibody titre (assessed by the fluorescence average (MFI) on Luminex beads) is involved in the risk of rejection but is far from explaining the disparities in clinical evolution.
DSA are mainly IgG of different subclasses whose distribution could have a major impact on their pathogenicity. Indeed, complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) functions differ according to IgG subclass. IgG3 is the subclass that has the greatest potential for complement activation followed by IgG1. IgG3 and IgG1 are also the two subclasses with the best affinities for the FcγRIIIa activating receptor for ADCC mediated by Natural Killer (NK) cells.
Some teams have shown that the detection of IgG3 anti-HLA by cytometry is associated with a higher risk of humoral rejection but these results have not been confirmed by others. One of the limitations of the cytometry by Luminex technique is that it only informs the detection of each subclass but does not allow analysis of the distribution of the different subclasses of a DSA.
A method has been developed for the relative detection and quantification of different subclasses of the DSA using the mass spectrometry technique and will be tested during this study. This new quantification method therefore opens up the prospect of studying whether, not only the presence but especially the distribution of IgG subclasses, in particular IgG3, could constitute a reliable and robust marker of humoral rejection.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| patient with kidney transplant | – | –Blood sample will be took from subjects during this research |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients 18 years old and over with kidney transplant and who have DSA
Key inclusion criteria (10 listed)
- - Patients over 18 years old
- Renal transplant patients followed at the University Hospital of Montpellier presenting a DSA de novo during follow-up.
- Affiliation or beneficiary of a social security scheme.
- Inclusion criteria specific to patients whose graft biopsy has already been performed
- Patients who consented to the collection of a plasma sample on graft biopsy day and use in future programs (Collection DC-2014-2328)
Key exclusion criteria (3 listed)
- Pregnant or lactating women according to Article L1121 5 of the health public Code
- Vulnerable persons according to article L1121-6 of the health public Code
- Major persons placed under guardianship or curator
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
distribution of DSA IgG subclasses
Time frame: day 0 (inclusion visit)
the performance of the distribution of DSA IgG subclasses for the diagnosis of humoral rejection in renal transplant patients with Donor Specific Antibodies
3 secondary outcomes
histological criteria for humoral rejection
Time frame: day 0 (inclusion visit)
degradation of graft function
Time frame: 1 year after inclusion of subjects
graft loss
Time frame: 1 year after inclusion of subjects
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2023.
- Results publication: PubMed 34863025Pernin V, Bec N, Beyze A, Bourgeois A, Szwarc I, Champion C, Chauvin A, Rene C, Mourad G, Merville P, Visentin J, Perrochia H, Couzi L, Larroque C, Le Quintrec M. IgG3 donor-specific antibodies with a proinflammatory glycosylation profile may be associated with the risk of antibody-mediated rejection after kidney transplantation. Am J Transplant. 2022 Mar;22(3):865-875. doi: 10.1111/ajt.16904. Epub 2021 Dec 18.
- Results publication: PubMed 32670261Pernin V, Beyze A, Szwarc I, Bec N, Salsac C, Perez-Garcia E, Mourad G, Merville P, Visentin J, Perrochia H, Larroque C, Couzi L, Le Quintrec M. Distribution of de novo Donor-Specific Antibody Subclasses Quantified by Mass Spectrometry: High IgG3 Proportion Is Associated With Antibody-Mediated Rejection Occurrence and Severity. Front Immunol. 2020 Jun 2;11:919. doi: 10.3389/fimmu.2020.00919. eCollection 2020.
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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. This study is not recruiting at the moment.
Vincent Pernin, Doctor principal investigator
UH Montpellier
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 Antibody-mediated Rejection, run by University Hospital, Montpellier 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 3 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: finished, as of the sponsor's last update on 23 Feb 2023. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
distribution of DSA IgG subclasses (time frame: day 0 (inclusion visit)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04026087, which also lists 2 linked publications.
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 23 Feb 2023.