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CD52‐negative T cells predict acute graft‐versus‐host disease after an alemtuzumab‐based conditioning regimen

2020; Wiley; Volume: 191; Issue: 2 Linguagem: Inglês

10.1111/bjh.16706

1365-2141

Pascal Woelfinger, Katharina Epp, Lukas Schaefer, Diana Kriege, Matthias Theobald, Tobias Bopp, Eva‐Maria Wagner‐Drouet,

T-cell and B-cell Immunology

Summary Allogeneic haematopoietic stem cell transplantation (HSCT) after a reduced‐intensity conditioning (RIC) regimen with fludarabine, melphalan and alemtuzmab is an effective therapy for haematological malignancies. Alemtuzumab, a monoclonal antibody against CD52, a glycosylphosphatidylinositol‐anchor‐bound surface protein on lymphocytes, depletes T cells to prevent graft‐versus‐host disease (GVHD). Despite this, acute and chronic GVHD (a/cGVHD) remain life‐threatening complications after HSCT. The aim of the present study was to identify parameters to predict GVHD. In 69 patients after HSCT, T‐cell subsets were functionally analysed. Reconstitution of CD52 neg T cells and CD52 neg regulatory T cells (Tregs) correlated with onset, severity and clinical course of aGVHD. Patients with aGVHD showed significantly lower levels of CD52 pos T cells compared to patients with cGVHD or without GVHD ( P < 0·001). Analysis of T‐cell reconstitution revealed a percentage of <40% of CD52 pos CD4 pos T cells or CD52 pos Tregs at day +50 as a risk factor for the development of aGVHD. In contrast, CD52 neg Tregs showed significant decreased levels of glycoprotein A repetitions predominant (GARP; P < 0·001), glucocorticoid‐induced TNFR‐related protein (GITR; P < 0·001), chemokine receptor (CXCR3; P = 0·023), C‐C chemokine receptor type 5 (CCR5; P = 0·004), but increased levels of immunoglobulin‐like transcript 3 (ILT3; P = 0·001), as well as a reduced suppressive capacity. We conclude that reconstitution of CD52 neg T cells and CD52 neg Tregs is a risk factor for development of aGVHD.