Quantitative Parameters of HLA-DQ Antibodies in Lung Transplantation

Recruiting

• Conditions: Antibody Mediated Rejection; Chronic Lung Allograft Dysfunction; Lung Transplantation

• Registration Number: NCT03474536
• Lead Sponsor: University Hospital, Bordeaux

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 .

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 Timeline

• Study First Submitted: 2018-03-05
• Study Start: 2018-03-14
• Study First Submitted QC: 2018-03-15
• Study First Posted: 2018-03-22
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-28
• Last Update Posted: 2025-03-30
• Primary Completion: 2025-04
• Study Completion: 2025-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 93

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
CLAD development	2 years	CLAD development within the 2 years following DSA apparition

Secondary Outcome Measures

Name	Time	Method
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	1 year	CLAD development 1 year following DSA apparition

Trial Locations

Locations (5)

Hôpital Marie Lannelongue; 🇫🇷 Le Plessis-Robinson, France

Hôpital Européen Georges Pompidou; 🇫🇷 Paris, France

AP-HP Hôpital Bichat; 🇫🇷 Paris, France

CHU Bordeaux; 🇫🇷 Bordeaux, France

Hôpital Foch; 🇫🇷 Suresnes, France