Quantitative Parameters of HLA-DQ Antibodies in Lung Transplantation

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Lung Transplantation, Antibody Mediated Rejection, Chronic Lung Allograft Dysfunction

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lung transplantation, HLA antibodies, concentration, affinity, surface plasmon resonance