AFFIHLA-P: Quantitative Parameters of HLA-DQ Antibodies in Lung Transplantation

Sponsor

University Hospital, Bordeaux (Other)

Overall Status

Completed

CT.gov ID

NCT03474536

Collaborator

(none)

Enrollment

Locations

Actual Duration (Months)

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The aim is to compare the quantitative parameters of de novo anti-HLA DQ Donor Specific Antibodies (DSA), determined at the time of their discovery by surface plasmon resonance (SPR), between recipients that developed a Chronic Lung Allograft Dysfunction (CLAD) for the 2 years following DSA apparition and those who did not. If concentration, kinetics and/or affinity parameters of anti-DQ DSA are associated with CLAD development, new, non-invasive prognostic biomarkers of humoral rejection in lung transplantation will be discovered .

Condition or Disease	Intervention/Treatment	Phase
Lung Transplantation Antibody Mediated Rejection Chronic Lung Allograft Dysfunction

Detailed Description

After lung transplantation the production of de novo DSA directed against HLA-DQ molecules is associated with CLAD and graft loss. The most used assay for serum DSA detection is the Single Antigen Luminex® (SAG), which provides a semi-quantitative fluorescence value, the MFI, used as a surrogate of DSA "strength". But MFI is not perfectly associated with CLAD development. We developed a method using SPR allowing the concentration, kinetics (ka, kd) and affinity parameters (KD) of anti-DQ DSA to be determined. These quantitative parameters could represent biomarkers finely associated with CLAD. The way this parameters evolve (stability, increase or decrease) with time could also impact on DSA pathogenicity. We will compare the quantitative parameters of de novo anti-HLA DQ DSA, determined at the time of their discovery, between recipients that developed a CLAD for the 2 years following DSA apparition, and those who did not. The association between quantitative parameters of DSA and graft loss, their evolution and its association with CLAD and graft loss, and their correlation with SAG MFI will be also evaluated.

Study Design

Study Type:

Observational

Actual Enrollment :

45 participants

Observational Model:

Cohort

Time Perspective:

Retrospective

Official Title:

Clinical Impact of Concentration and Affinity of HLA-DQ Antibodies in Lung Transplantation - AFFIHLA-P

Actual Study Start Date :

Mar 14, 2018

Actual Primary Completion Date :

Dec 13, 2019

Actual Study Completion Date :

Dec 13, 2019

Outcome Measures

Primary Outcome Measures

CLAD development [2 years]
CLAD development within the 2 years following DSA apparition

Secondary Outcome Measures

raft loss up to 5 years following DSA apparition [6 months, 1 year, 2 years, 5 years]
Graft loss up to 5 years following DSA apparition, defined by re-transplantation or recipient's death
CLAD development [6 months]
CLAD development 6 months following DSA apparition
CLAD development [1 year]
CLAD development 1 year following DSA apparition

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 18 years and older
Patient transplanted between 01/01/2001 and 31/07/2016
Patient with immunodominant anti-HLA DQ de novo DSA developed before 08/2016
Patient for who sufficient remaining serum quantity is available in usual care biobank
non-opposition of the patient

Exclusion Criteria:

preformed DSA at the transplantation;
Non immunodominant DQ DSA ;
Insufficient serum quantity in usual care biobank
Inability to determine the date of DSA apparition at around one year
opposition of the patient

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	CHU Bordeaux	Bordeaux	France
2	Hôpital Marie Lannelongue	Le Plessis-Robinson	France	92350
3	Hôpital Européen Georges Pompidou	Paris	France	75015
4	AP-HP Hôpital Bichat	Paris	France	75877
5	Hôpital Foch	Suresnes	France	92150

Sponsors and Collaborators

University Hospital, Bordeaux

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

University Hospital, Bordeaux

ClinicalTrials.gov Identifier:

NCT03474536

Other Study ID Numbers:

CHUBX 2017/35

First Posted:

Mar 22, 2018

Last Update Posted:

Apr 29, 2020

Last Verified:

Apr 1, 2020

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by University Hospital, Bordeaux

surface plasmon resonance

Study Results

No Results Posted as of Apr 29, 2020