Quantitative Parameters of HLA-DQ Antibodies in Lung Transplantation

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

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT03474536

Acronym

AFFIHLA-P

Enrollment

Registered

2018-03-22

Start date

2018-03-14

Completion date

2025-04-08

Last updated

2025-07-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Antibody Mediated Rejection, Chronic Lung Allograft Dysfunction, Lung Transplantation

Keywords

Lung transplantation, HLA antibodies, concentration, affinity, surface plasmon resonance

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.

Interventions

None listed

Study design

Observational model

COHORT

Time perspective

RETROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

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

Design outcomes

Primary

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

Secondary

Measure	Time frame	Description
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

Countries

France

Outcome results