Correspondence

Multiple Autoimmune Diseases after Autologous Stem-Cell Transplantation

N Engl J Med 2007; 357:2734-2736December 27, 2007

Article

To the Editor:

Hematopoietic stem-cell transplantation can be an effective treatment in patients with refractory systemic sclerosis.1 We report on a 19-year-old woman with systemic sclerosis who underwent CD34+-selected autologous hematopoietic stem-cell transplantation in March 2001. Before the transplantation, the physical and laboratory findings showed no evidence of any other autoimmune diseases. After written consent was obtained from the patient, CD34+ hematopoietic stem cells were transplanted according to a method used for systemic sclerosis.1 The dermal sclerosis improved immediately after transplantation, but thrombocytopenia and Graves' disease developed.

In June 2005, the patient was admitted to the hospital because of fever and edema. Blood tests revealed proteinuria (11.4 g per day) and new autoantibodies in the serum (Figure 1AFigure 1Clinical and Laboratory Findings after CD34+-Selected Autologous Hematopoietic Stem-Cell Transplantation.). On the sixth hospital day, paralysis developed on the left side as the result of a right cerebral infarction. Systemic lupus erythematosus with membranous-type lupus nephritis (Figure 2Figure 2Renal-Biopsy Specimens Showing Representative Lesions at the Onset of Lupus Nephritis.) and the antiphospholipid-antibody syndrome were diagnosed; the patient was treated with prednisolone, warfarin, and cyclosporine. She is currently in clinical remission and is back at work.

During the early phases of immune reconstitution, residual lymphocytes undergo proliferation and expansion, a process controlled by regulatory T cells.2,3 These cells, defined by the phenotype CD4+CD25+FOXP3+, are important in the prevention of autoimmunity. Interleukin-17–producing helper T (Th17) cells may play a role in the induction of autoimmunity.4,5 In our patient, the level of serum interleukin-17, released mainly by Th17 cells, was elevated at the onset of the systemic lupus (Figure 1B). Levels of FOXP3 messenger RNA, a marker of regulatory T cells, were reduced, suggesting a deficiency of such cells (Figure 1C). The findings in our patient suggest a role of both regulatory T cells and Th17 in the development of systemic lupus.

Toshiyuki Bohgaki, M.D., Ph.D.
Tatsuya Atsumi, M.D., Ph.D.
Takao Koike, M.D., Ph.D.
Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan
tbohgaki@uhnres.utoronto.ca

5 References

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Citing Articles (6)

Citing Articles

1. 1

   T. Daikeler, M. Labopin, M. Di Gioia, M. Abinun, T. Alexander, I. Miniati, F. Gualandi, A. Fassas, T. Martin, C. P. Schwarze, N. Wulffraat, M. Buch, A. Sampol, E. Carreras, B. Dubois, B. Gruhn, T. Gungor, D. Pohlreich, A. Schuerwegh, E. Snarski, J. Snowden, P. Veys, A. Fasth, S. Lenhoff, C. Messina, J. Voswinkel, M. Badoglio, J. Henes, D. Launay, A. Tyndall, E. Gluckman, D. Farge, . (2011) Secondary autoimmune diseases occurring after HSCT for an autoimmune disease: a retrospective study of the EBMT Autoimmune Disease Working Party. Blood 118:6, 1693-1698
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2. 2

   A.B. Farris, D. Taheri, T. Kawai, L. Fazlollahi, W. Wong, N. Tolkoff-Rubin, T. R. Spitzer, A. J. Iafrate, F. I. Preffer, S. A. LoCascio, B. Sprangers, S. Saidman, R. N. Smith, A. B. Cosimi, M. Sykes, D. H. Sachs, R. B. Colvin. (2011) Acute Renal Endothelial Injury During Marrow Recovery in a Cohort of Combined Kidney and Bone Marrow Allografts. American Journal of Transplantation 11:7, 1464-1477
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   Christophe Deligny, Emmanuel Clave, David Sibon, Thomas Daikeler, Homah Keshmandt, Maryvonnic Carmagnat, Corinne Douay, Serge Arfi, Bernard Clair, Antoine Toubert, Dominique Farge. (2010) New onset of myasthenia gravis after treatment of systemic sclerosis by autologous hematopoietic stem cell transplantation: Sustained autoimmunity or inadequate reset of tolerance?. Human Immunology 71:4, 363-365
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4. 4

   Cheryl C.M. Barnabe, Sharon A. LeClercq, Avril A. Fitzgerald. (2009) The Development of Inflammatory Arthritis and Other Rheumatic Diseases Following Stem Cell Transplantation. Seminars in Arthritis and Rheumatism 39:1, 55-60
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5. 5

   Alan Tyndall, Alois Gratwohl. (2009) Adult stem cell transplantation in autoimmune disease. Current Opinion in Hematology 16:4, 285-291
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6. 6

   T Daikeler, T Hügle, D Farge, M Andolina, F Gualandi, H Baldomero, C Bocelli-Tyndall, M Brune, J H Dalle, G Ehninger, B Gibson, B Linder, B Lioure, A Marmont, S Matthes-Martin, D Nachbaur, P Schuetz, A Tyndall, J M van Laar, P Veys, R Saccardi, A Gratwohl. (2009) Allogeneic hematopoietic SCT for patients with autoimmune diseases. Bone Marrow Transplantation 44:1, 27-33
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