DO MESENCHYMAL STROMAL CELLS PROMOTE HLA SPECIFIC ANTIBODIES FORMATION AFTER INFUSION IN LIVER TRANSPLANT RECIPIENTS?

Background: Mesenchymal stromal cells (MSC) immunogenicity is debated. We recently published a prospective, controlled, phase I study evaluating a single administration of third-party MSC in 10 liver transplant recipients (LTR). Here, we focus on the development of antibodies (Ab) against MSC-donor HLA (MSCDSA) in LTR following MSC infusion.
Methods: Ten LTR under standard immunosuppression received 3rd-party unrelated MSC on postoperative day 3, and were prospectively compared to 10 control LTR. Recipients and donor of either liver or MSC were genotyped for HLA A/B/C/DR/DQ. Recipients were tested for HLA Ab before and 1, 3 and 6 months after transplant by Luminex". Ab were considered as positive in case of MFI >1500 and in accordance with the manufacturer’s recommendations. Results: In MSC-treated group, 2 patients showed pre-transplant MSCDSA. During follow-up, MSCDSA were detected in 6 additional patients who had received multiple red blood cell allo-transfusions before and/or rapidly after transplant. These patients also developed Ab against various MSC-unrelatedHLA. Two patients did not develop any MSCDSA throughout the follow-up, and one of them did not receive any allo-transfusion. MFI of detected MSCDSA were not significantly different from MFI of other detected HLA Ab. In control group, 3 patients were sensitized pre-transplant, and 6 patients developed de novo multiple HLA Ab. Four of these had received multiple allo-transfusions. Conclusion: In the large pool of HLA Ab identified in LTR post transplant, the detection of MSCDSA is most likely caused by allo-transfusions rather than related to MSC infusion. Further studies are required to confirm that MSC are “immune privileged”.