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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

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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.

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Acknowledgements

The project was supported by a grant from the German José Carreras Foundation. In addition, Daniel Wolff and Ernst Holler have been supported by a grant from the German José Carreras Foundation project “GVHD Competence Center Regensburg.” Ute Fehn was supported by a grant from the Regensburg Center of Interventional Immunology. The authors want to thank M. Köhler, R. Eder, and M. Germeroth for conducting flow cytometry. The authors want to thank Philipp York Herzberg from the Helmut Schmidt University of the Federal Armed Forces Hamburg (Germany) for support in performing the multivariate analysis.

Author’s contribution

E.-M. Bohmann performed the statistical analysis and wrote the manuscript.

U. Fehn performed the measurements.

B. Holler recruited the patients and documented the clinical data.

D. Weber recruited the patients and documented the clinical data.

E. Holler designed the study and corrected the manuscript.

W. Herr contributed to the design of trial, correction of manuscript, and discussion of results.

P. Hoffmann contributed to the manuscript and performed the analyses.

M. Edinger contributed to the trial design and manuscript and provided technical equipment.

D. Wolff developed the trial design, supervised the analyses, and corrected the manuscript.

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Authors and Affiliations

  1. Department of Internal Medicine III, University Hospital of Regensburg, F.J. Strauss Allee 11, 93053, Regensburg, Germany

    E.-M. Bohmann, U. Fehn, B. Holler, D. Weber, E. Holler, W. Herr, P. Hoffmann, M. Edinger & D. Wolff

  2. Regensburg Center for Interventional Immunology, University of Regensburg, Regensburg, Germany

    U. Fehn, E. Holler, P. Hoffmann, M. Edinger & D. Wolff

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  1. E.-M. Bohmann
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  2. U. Fehn
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  3. B. Holler
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  4. D. Weber
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  5. E. Holler
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  6. W. Herr
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  7. P. Hoffmann
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  8. M. Edinger
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  9. D. Wolff
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Corresponding author

Correspondence to D. Wolff.

Ethics declarations

From February 2009 until September 2012, all consecutive patients matching the inclusion criteria (informed consent, available sample) undergoing alloHSCT at the Department of Medicine III at the University Hospital Regensburg were included into the prospective study that was conducted in accordance with the Declaration of Helsinki and had been approved by the local ethics committee.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

M. Edinger and D. Wolff contributed equally to the manuscript.

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Bohmann, EM., Fehn, U., Holler, B. et al. 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. Ann Hematol 96, 299–310 (2017). https://doi.org/10.1007/s00277-016-2881-x

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  • DOI: https://doi.org/10.1007/s00277-016-2881-x

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