Quantitative Parameters of HLA-DQ Antibodies in Lung Transplantation

Lung Transplantation Clinical Trial

— AFFIHLA-P  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03474536
• Other study ID #: CHUBX 2017/35
• Status: Recruiting
• Start date: March 14, 2018
• Est. completion date: December 13, 2024

Study information

• Verified date: May 2024
• Source: University Hospital, Bordeaux
• Contact: Jonathan Visentin, MD, Ph.D
• Phone: +33557 82 08 85
• Email: jonathan.visentin[@]chu-bordeaux.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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 .

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 93
• Est. completion date: December 13, 2024
• Est. primary completion date: December 13, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Antibody Mediated Rejection
• Chronic Lung Allograft Dysfunction
• Lung Transplantation

Locations

Country	Name	City	State
France	CHU Bordeaux	Bordeaux
France	Hôpital Marie Lannelongue	Le Plessis-Robinson
France	AP-HP Hôpital Bichat	Paris
France	Hôpital Européen Georges Pompidou	Paris
France	Hôpital Foch	Suresnes

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Bordeaux

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CLAD development	CLAD development within the 2 years following DSA apparition	2 years
Secondary	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
Secondary	CLAD development	CLAD development 6 months following DSA apparition	6 months
Secondary	CLAD development	CLAD development 1 year following DSA apparition	1 year