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CD52‐negative T cells predict acute graft‐versus‐host disease after an alemtuzumab‐based conditioning regimen
Author(s) -
Woelfinger Pascal,
Epp Katharina,
Schaefer Lukas,
Kriege Diana,
Theobald Matthias,
Bopp Tobias,
WagnerDrouet EvaMaria
Publication year - 2020
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.16706
Subject(s) - cd52 , alemtuzumab , medicine , immunology , hematopoietic stem cell transplantation , t cell , transplantation , antibody , immune system
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.