title: Altered immune reconstitution of B and T cells precedes the onset of clinical symptoms of chronic graft-versus-host disease and is influenced by the type of onset.
abstract: We analyzed lymphocyte subpopulations and cytokines 3 months after allogeneic hematopoietic stem cell transplantation aiming to identify predictive cellular and serum markers for chronic graft-versus-host disease (cGVHD). Samples of 49 patients (pts) (no cGVHD (n = 14), subsequent quiescent onset (n = 16), de novo onset of cGVHD (n = 19)) were analyzed in the absence of active GVHD by flow cytometry and enzyme-linked immunosorbent assay. All mean absolute cell counts are presented as cells per microliter; relative cell counts are presented as percentage of lymphocytes. Pts with subsequent de novo cGVHD had significantly higher relative and absolute counts of CD4+ T cells including higher absolute counts of CD4+ memory T cells (22.36%; 206.55/μl; 136/μl, respectively) compared to pts with subsequent quiescent onset of cGVHD (12.41%; 83.42/μl; 54.3/μl) and pts without cGVHD (10.55%) with regard to relative counts of CD4+ T cells. Similarly, significantly more relative and absolute regulatory T cell numbers (CD4+FOXP3+) were detected in pts with de novo onset of cGVHD (3.08% and 24.63/μl) compared to those in pts without (1.25% and 9.06/μl) or with quiescent onset of cGVHD (1.15% and 6.91/μl). Finally, relative B cell counts, including naïve and memory B cells, were also significantly decreased in pts developing quiescent cGVHD (0.85, 0.73, 0.12% resp.) when compared to pts with de novo onset (5.61, 5.24, 0.38%). The results demonstrate that alterations in immune reconstitution are already present before onset of clinical symptoms and differ between de novo and quiescent onset of disease.
authors.affiliation: Department of Internal Medicine III, University Hospital of Regensburg, F.J. Strauss Allee 11, 93053, Regensburg, Germany.
authors.forename: E-M
authors.initials: EM
authors.lastname: Bohmann
authors.affiliation: Department of Internal Medicine III, University Hospital of Regensburg, F.J. Strauss Allee 11, 93053, Regensburg, Germany.|Regensburg Center for Interventional Immunology, University of Regensburg, Regensburg, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Fehn
authors.affiliation: Department of Internal Medicine III, University Hospital of Regensburg, F.J. Strauss Allee 11, 93053, Regensburg, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Holler
authors.affiliation: Department of Internal Medicine III, University Hospital of Regensburg, F.J. Strauss Allee 11, 93053, Regensburg, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Weber
authors.affiliation: Department of Internal Medicine III, University Hospital of Regensburg, F.J. Strauss Allee 11, 93053, Regensburg, Germany.|Regensburg Center for Interventional Immunology, University of Regensburg, Regensburg, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Holler
authors.affiliation: Department of Internal Medicine III, University Hospital of Regensburg, F.J. Strauss Allee 11, 93053, Regensburg, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Herr
authors.affiliation: Department of Internal Medicine III, University Hospital of Regensburg, F.J. Strauss Allee 11, 93053, Regensburg, Germany.|Regensburg Center for Interventional Immunology, University of Regensburg, Regensburg, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Hoffmann
authors.affiliation: Department of Internal Medicine III, University Hospital of Regensburg, F.J. Strauss Allee 11, 93053, Regensburg, Germany.|Regensburg Center for Interventional Immunology, University of Regensburg, Regensburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Edinger
authors.affiliation: Department of Internal Medicine III, University Hospital of Regensburg, F.J. Strauss Allee 11, 93053, Regensburg, Germany. daniel.wolff@ukr.de.|Regensburg Center for Interventional Immunology, University of Regensburg, Regensburg, Germany. daniel.wolff@ukr.de.
authors.forename: D
authors.identifier: http://orcid.org/0000-0001-7015-3190
authors.initials: D
authors.lastname: Wolff
mesh_terms: D000293:Adolescent; D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000097:blood / Q000276:immunology; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood / Q000175:diagnosis* / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000639:trends*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013997:Time Factors; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000639:trends; D055815:Young Adult
chemical_list: D016207:Cytokines
keywords: Allogeneic hematopoietic stem cell transplantation; BAFF; Bone marrow transplantation; Graft-versus-host disease; Immature B cells