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

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

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 .

Study Overview

• Status: Completed
• Conditions: 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 Type: Observational
• Enrollment (Actual): 88

Contacts and Locations

Study Locations

• France
  • Bordeaux, France
    • Chu Bordeaux
  • Le Plessis-Robinson, France, 92350
    • Hopital Marie Lannelongue
  • Paris, France, 75015
    • Hopital Europeen Georges Pompidou
  • Paris, France, 75877
    • AP-HP Hôpital Bichat
  • Suresnes, France, 92150
    • Hopital Foch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

122 patients with lung transplantation at University Hospital of Bordeaux and 4 departments of lung transplantation from Paris (Marie Lannelongue, Foch, Bichat and HEGP hospitals

Description

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 Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CLAD development	CLAD development within the 2 years following DSA apparition	2 years

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2018
• Primary Completion (Actual): April 8, 2025
• Study Completion (Actual): April 8, 2025

Study Registration Dates

• First Submitted: March 5, 2018
• First Submitted That Met QC Criteria: March 15, 2018
• First Posted (Actual): March 22, 2018

Study Record Updates

• Last Update Posted (Actual): July 4, 2025
• Last Update Submitted That Met QC Criteria: July 1, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Lung transplantation; concentration; HLA antibodies; affinity; surface plasmon resonance
• Other Study ID Numbers: CHUBX 2017/35

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No