Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Graft-versus-host Disease

Cerebral angiitis in four patients with chronic GVHD

Bone Marrow Transplantation volume 45, pages 1181–1188 (2010)Cite this article

Abstract

There is growing evidence that GVHD affects the central nervous system (CNS). In this study, we describe the long-term follow-up of four allogeneic BM recipients who developed cerebral angiitis-like disease probably due to GVHD. The patients developed focal neurological signs, cognitive deficits and/or coma in association with GVHD, 2–18 years after transplantation, following reduction of immunosuppressive therapy. Magnetic resonance imaging was variable, showing generalized brain atrophy, ischemic lesions or leukoencephalopathy. Diagnosis of cerebral angiitis was confirmed by histopathological analysis of bioptic brain tissue and response to immunosuppressive therapy. By means of immunohistochemistry and immunofluorescence, perivascular lymphomononuclear cerebral infiltrates were shown to express the adhesion receptor, CD11a, and the chemokine receptor, CCR5. Our findings imply that GVHD should be considered in the differential diagnosis of noninfectious angiitis-like disease of the CNS in long-term survivors after allogeneic BMT. Infiltrating cells, in analogy to typical target organs of GVHD such as skin or liver, expressed CD11a and CCR5. These findings could be of etiopathological, diagnostic and therapeutic relevance.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. de Brabander C, Cornelissen J, Smitt PA, Vecht CJ, van den Bent MJ . Increased incidence of neurological complications in patients receiving an allogenic bone marrow transplantation from alternative donors. J Neurol Neurosurg Psychiatry 2000; 68: 36–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Gallardo D, Ferra C, Berlanga JJ, Banda ED, Ponce C, Salar A et al. Neurologic complications after allogeneic bone marrow transplantation. Bone Marrow Transplant 1996; 18: 1135–1139.

    CAS  PubMed  Google Scholar 

  3. Sostak P, Padovan CS, Yousry TA, Ledderose G, Kolb HJ, Straube A . Prospective evaluation of neurological complications after allogeneic bone marrow transplantation. Neurology 2003; 60: 842–848.

    Article  CAS  PubMed  Google Scholar 

  4. Antonini G, Ceschin V, Morino S, Fiorelli M, Gragnani F, Mengarelli A et al. Early neurologic complications following allogeneic bone marrow transplant for leukemia: A prospective study. Neurology 1998; 50: 1441–1445.

    Article  CAS  PubMed  Google Scholar 

  5. Campellone JV, Lacomis D . Neuromuscular disorders. In: Wijdicks EFM (ed). Neurological Complications in Organ Transplant Recipients 1999 1st edn. Butterworth Heinemann: Boston, pp 169–192.

    Google Scholar 

  6. Padovan CS, Yousry TA, Schleuning M . Neurological and neuroradiological findings in long-term survivors of allogeneic bone marrow transplantation. Ann Neurol 1998; 43: 627–633.

    Article  CAS  PubMed  Google Scholar 

  7. Campbell JN, Morris PP . Cerebral vasculitis in graft-versus-host disease: a case report. AJNR Am J Neuroradiol 2005; 26: 654–656.

    PubMed  PubMed Central  Google Scholar 

  8. Iwasaki Y, Sako K, Ohara Y, Miyazawa M, Minegishi M, Tsuchiya S et al. Subacute panencephalitis associated with chronic graft-versus-host disease. Acta Neuropathol (Berl) 1993; 85: 566–572.

    CAS  Google Scholar 

  9. Kamble RT, Chang CC, Sanchez S, Carrum G . Central nervous system graft-versus-host disease: report of two cases and literature review. Bone Marrow Transplant 2007; 39: 49–52.

    Article  CAS  PubMed  Google Scholar 

  10. Kew AK, Macaulay R, Burrell S, Rubin S, Dow G, Couban S . Central nervous system graft-versus-host disease presenting with granulomatous encephalitis. Bone Marrow Transplant 2007; 40: 183–184.

    Article  CAS  PubMed  Google Scholar 

  11. Ma M, Barnes G, Pulliam J, Jezek D, Baumann RJ, Berger JR . CNS angiitis in graft vs host disease. Neurology 2002; 59: 1994–1997.

    Article  CAS  PubMed  Google Scholar 

  12. Marosi C, Budka H, Grimm G, Zeitlhofer J, Sluga E, Brunner C et al. Fatal encephalitis in a patient with chronic graft-versus-host disease. Bone Marrow Transplant 1990; 6: 53–57.

    CAS  PubMed  Google Scholar 

  13. Padovan CS, Bise K, Hahn J, Sostak P, Holler E, Kolb HJ et al. Angiitis of the central nervous system after allogeneic bone marrow transplantation? Stroke 1999; 30: 1651–1656.

    Article  CAS  PubMed  Google Scholar 

  14. Filipovich AH . Diagnosis and manifestations of chronic graft-versus-host disease. Best Pract Res Clin Haematol 2008; 21: 251–257.

    Article  CAS  PubMed  Google Scholar 

  15. Sostak P, Reich P, Padovan CS, Gerbitz A, Holler E, Straube A . Cerebral endothelial expression of adhesion molecules in mice with chronic graft-versus-host disease. Stroke 2004; 35: 1158–1163.

    Article  CAS  PubMed  Google Scholar 

  16. Tornehave D, Hougaard DM, Larsson L . Microwaving for double indirect immunofluorescence with primary antibodies from the same species and for staining of mouse tissues with mouse monoclonal antibodies. Histochem Cell Biol 2000; 113: 19–23.

    Article  CAS  PubMed  Google Scholar 

  17. Sostak P, Theil D, Stepp H, Roeber S, Kretzschmar HA, Straube A . Detection of bone marrow-derived cells expressing a neural phenotype in the human brain. J Neuropathol Exp Neurol 2007; 66: 110–116.

    Article  PubMed  Google Scholar 

  18. Genovese E, Maghnie M, Maggiore G, Tinelli C, Lizzoli F, De Giacomo C et al. MR imaging of CNS involvement in children affected by chronic liver disease. AJNR Am J Neuroradiol 2000; 21: 845–851.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Vollmer TL, Guarnaccia J, Harrington W, Pacia SV, Petroff OA . Idiopathic granulomatous angiitis of the central nervous system. Diagnostic challenges. Arch Neurol 1993; 50: 925–930.

    Article  CAS  PubMed  Google Scholar 

  20. Mohrmann RL, Mah V, Vinters HV . Neuropathologic findings after bone marrow transplantation: an autopsy study. Hum Pathol 1990; 21: 630–639.

    Article  CAS  PubMed  Google Scholar 

  21. Patchell RA, White CL, Clark AW, Beschorner WE, Santos GW . Neurologic complications of bone marrow transplantation. Neurology 1985; 35: 300–306.

    Article  CAS  PubMed  Google Scholar 

  22. Kajiwara K, Hirozane A, Fukumoto T, Orita T, Nishizaki T, Kamiryo T et al. Major histocompatibility complex expression in brain of rats with graft-versus-host disease. J Neuroimmunol 1991; 32: 191–198.

    Article  CAS  PubMed  Google Scholar 

  23. Hickey WF, Vass K, Lassmann H . Bone marrow-derived elements in the central nervous system: an immunohistochemical and ultrastructural survey of rat chimeras. J Neuropathol Exp Neurol 1992; 51: 246–256.

    Article  CAS  PubMed  Google Scholar 

  24. Padovan CS, Gerbitz A, Sostak P, Holler E, Ferrara JL, Bise K et al. Cerebral involvement in graft-versus-host disease after murine bone marrow transplantation. Neurology 2001; 56: 1106–1108.

    Article  CAS  PubMed  Google Scholar 

  25. Brown KA . Factors modifying the migration of lymphocytes across the blood-brain barrier. Int Immunopharmacol 2001; 1: 2043–2062.

    Article  CAS  PubMed  Google Scholar 

  26. Balashov KE, Rottman JB, Weiner HL, Hancock WW . CCR5(+) and CXCR3(+) T cells are increased in multiple sclerosis and their ligands MIP-1alpha and IP-10 are expressed in demyelinating brain lesions. Proc Natl Acad Sci USA 1999; 96: 6873–6878.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Zhang Y, McCormick LL, Desai SR, Wu C, Gilliam AC . Murine sclerodermatous graft-versus-host disease, a model for human scleroderma: cutaneous cytokines, chemokines, and immune cell activation. J Immunol 2002; 168: 3088–3098.

    Article  CAS  PubMed  Google Scholar 

  28. New JY, Li B, Koh WP, Ng HK, Tan SY, Yap EH et al. T cell infiltration and chemokine expression: relevance to the disease localization in murine graft-versus-host disease. Bone Marrow Transplant 2002; 29: 979–986.

    Article  CAS  PubMed  Google Scholar 

  29. Morita NI, Matsumura Y, Morita K, Miyachi Y . Expression of CCR5 in graft-versus-host disease (GVHD) of the skin: immunohistochemical staining of 38 cases. J Dermatol 2007; 34: 254–257.

    Article  PubMed  Google Scholar 

  30. Wysocki CA, Burkett SB, Panoskaltsis-Mortari A, Kirby SL, Luster AD, McKinnon K et al. Differential roles for CCR5 expression on donor T cells during graft-versus-host disease based on pretransplant conditioning. J Immunol 2004; 173: 845–854.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank K Ogston for copyediting the paper and A Henn, S Langer and J Mandelbaum for technical assistance. This work was supported by the Deutsche Forschungsgemeinschaft SO825 (to PS) and by the Hartmann Müller Stiftung (S Segerer).

Author information

Authors and Affiliations

  1. Department of Neurology, Klinikum Großhadern, Ludwig Maximilian University, Munich, Germany

    P Sostak, C S Padovan, C Schankin, D Theil & A Straube

  2. Center for Neuropathology and Prion Research, Ludwig Maximilian University, Munich, Germany

    S Eigenbrod, S Roeber & H Kretzschmar

  3. Clinic for Nephrology, University Hospital, Zürich, Switzerland

    S Segerer

  4. Institute of Anatomy, University of Zürich, Zürich, Switzerland

    S Segerer

  5. Department of Pathology, Klinikum Großhadern, Ludwig Maximilian University, Munich, Germany

    S Siegert

  6. Department of Clinical Radiology, Klinikum Großhadern, Ludwig Maximilian University, Munich, Germany

    T Saam

  7. Department of Internal Medicine III, Klinikum Großhadern, Ludwig Maximilian University, Munich, Germany

    H-J Kolb

Authors
  1. P Sostak
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C S Padovan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S Eigenbrod
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S Roeber
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S Segerer
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. C Schankin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. S Siegert
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. T Saam
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. D Theil
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. H-J Kolb
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. H Kretzschmar
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. A Straube
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P Sostak.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies the paper on Bone Marrow Transplantation website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sostak, P., Padovan, C., Eigenbrod, S. et al. Cerebral angiitis in four patients with chronic GVHD. Bone Marrow Transplant 45, 1181–1188 (2010). https://doi.org/10.1038/bmt.2009.323

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2009.323

Keywords

This article is cited by

Search

Advanced search

Quick links