Clinical trial NCT03474536: Quantitative Parameters of HLA-DQ Antibodies in Lung Transplantation
Official title: Clinical Impact of Concentration and Affinity of HLA-DQ Antibodies in Lung Transplantation - AFFIHLA-P
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Lung Transplantation
Antibody Mediated Rejection
Chronic Lung Allograft Dysfunction
Keywords: Lung transplantation
HLA antibodies
concentration
affinity
surface plasmon resonance
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2018-03-22
Enrollment: 93
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
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

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.

Eligibility criteria: 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

Primary outcomes:
measure: CLAD development
timeFrame: 2 years
Secondary outcomes:
measure: raft loss up to 5 years following DSA apparition
timeFrame: 6 months, 1 year, 2 years, 5 years
measure: CLAD development
timeFrame: 6 months
measure: CLAD development
timeFrame: 1 year
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: CHU Bordeaux
city: Le Plessis-Robinson
country: France
facility: Hôpital Marie Lannelongue
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
city: Paris
country: France
facility: AP-HP Hôpital Bichat
city: Suresnes
country: France
facility: Hôpital Foch
Study officials:
References: