The occurrence of chronic lung allograft dysfunction (CLAD) is the main complication after lung transplantation (LT) and remains the most common cause of graft failure and death. Currently, the available immunosuppressive therapies cannot prevent its occurrence in 50% of patients at 5 years. Conversely, some LT recipients, remain free of CLAD for a long time, and are considered as stable (STA). Whereas in kidney transplantation, predictive B-cell signature of long term or poor graft outcome have been identified by us and others, nothing has been done yet in lung transplantation. We aim to identify and validate predictive B lymphocyte signatures in order to identify and lighten the risk of CLAD and allow for early intervention before irreversible damages.

PBMCs from the Lung Transplanted patients (COLT) COhort were immunophenotyped before LT, one month after LT, at the visit for which CLAD was diagnosed, 6 months before and 6 months after CLAD. PBMCs from patients with long-term functional stability (STA) and healthy volunteers (HV) were analyzed as controls. Cells were stained for the B-cell markers CD19, CD27, CD38, CD138, CD22, CD24, IgD, IgM, CD5 and CD9 to determine the percentage of transitional, naive, plasmablast, memory and regulatory B-cells.

No difference was observed for total CD19+ B cells, memory, naïve, and plasma cells between the three groups of patients at the different time points. However, 18 months after LT, STA increased their level of transitional B cells to almost reach the physiological level similar to HV (2.25% vs 3.1 respectively) while it stays very low in rejecting patients (1.1%). These transitional were CD24hiCD38hiIgDhiIgMhi characteristic of the T2 transitional regulatory subset, expressed the CD5 and CD9 regulatory markers and secrete IL-10+. Finally, the rate of transitional was predictive of the CLAD 6 months before and was associated with a better survival of the graft.

These data show that a decreased level of CD24hiCD38hiIgDhiIgMh transitional B cells with a regulatory phenotype is predictive of CLAD (6 months before) and is associated with a poor grant survival of 5 years post-transplantation. Such biomarkers would allow early recognition and specific intervention in patients at risk of CLAD and would undoubtedly improve outcomes.

CITATION INFORMATION: Brosseau C, Durand M, Durand E, Loy J, Foureau A, Lacoste P, Royer P.-J, Magnan A, Brouard S. Characterization of a B Lymphocyte Signature Predictive of Chronic Lung Allograft Dysfunction. Am J Transplant. 2017;17 (suppl 3).

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