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Post-Transplant Events

Immune recovery after autologous PBSC transplantation without in vitro graft manipulation for refractory systemic lupus erythematosus

Abstract

Autologous hematopoietic SCT (ASCT) has been investigated as salvage therapy for refractory systemic lupus erythematosus (SLE). Although immune recovery after ASCT with in vitro purging of lymphocytes has been extensively studied, little information is available about immune recovery after ASCT without in vitro purging. Therefore, we analyzed the immune recovery of a patient who successfully underwent ASCT without in vitro purging for refractory SLE. In addition to the numbers of PBL subsets, T-cell receptor rearrangement excision circles (TRECs) and the T-cell receptor repertoire diversity of both CD4+ and CD8+ T cells were sequentially analyzed. All SLE-related symptoms disappeared within 3 months after ASCT and the serum anti-dsDNA Ab became undetectable. The number of CD4+CD45RO+ memory T cells remained lower than that in healthy adult controls, but the number of CD4+CD45RA+ naïve T cells showed a rapid increase after ASCT. TRECs of both CD4+ and CD8+ T cells were strongly suppressed before ASCT, but consistently increased after ASCT. The T-cell receptor repertoire of CD8+ T cells was skewed before ASCT, but the diversity recovered after ASCT. ASCT with the reinfusion of a large number of autologous T cells did not impair the recovery of naive T cells or resetting of the immune system.

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References

  1. Burt RK, Traynor A, Statkute L, Barr WG, Rosa R, Schroeder J et al. Nonmyeloablative hematopoietic stem cell transplantation for systemic lupus erythematosus. JAMA 2006; 295: 527–535.

    Article  CAS  Google Scholar 

  2. Farge D, Labopin M, Tyndall A, Fassas A, Mancardi GL, Van Laar J et al. Autologous hematopoietic stem cell transplantation for autoimmune diseases: an observational study on 12 years’ experience from the European Group for Blood and Marrow Transplantation Working Party on Autoimmune Diseases. Haematologica 2010; 95: 284–292.

    Article  Google Scholar 

  3. Kohno K, Nagafuji K, Tsukamoto H, Horiuchi T, Takase K, Aoki K et al. Infectious complications in patients receiving autologous CD34-selected hematopoietic stem cell transplantation for severe autoimmune diseases. Transpl Infect Dis 2009; 11: 318–323.

    Article  CAS  PubMed  Google Scholar 

  4. Alexander T, Thiel A, Rosen O, Massenkeil G, Sattler A, Kohler S et al. Depletion of autoreactive immunologic memory followed by autologous hematopoietic stem cell transplantation in patients with refractory SLE induces long-term remission through de novo generation of a juvenile and tolerant immune system. Blood 2009; 113: 214–223.

    Article  CAS  PubMed  Google Scholar 

  5. Muraro PA, Douek DC, Packer A, Chung G, Guenaga FJ, Cassiani-Ingoni R et al. Thymic output generates a new and diverse TCR repertoire after autologous stem cell transplantation in multiple sclerosis patients. J Exp Med 2005; 201: 805–816.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. McFarland RD, Douek DC, Koup RA, Picker LJ . Identification of a human recent thymic emigrant phenotype. Proc Natl Acad Sci USA 2000; 97: 4215–4220.

    Article  CAS  PubMed  Google Scholar 

  7. Zeng W, Nakao S, Takamatsu H, Yachie A, Takami A, Kondo Y et al. Characterization of T-cell repertoire of the bone marrow in immune-mediated aplastic anemia: evidence for the involvement of antigen-driven T-cell response in cyclosporine-dependent aplastic anemia. Blood 1999; 93: 3008–3016.

    CAS  PubMed  Google Scholar 

  8. Labrecque N, McGrath H, Subramanyam M, Huber BT, Sekaly RP . Human T cells respond to mouse mammary tumor virus-encoded superantigen: V beta restriction and conserved evolutionary features. J Exp Med 1993; 177: 1735–1743.

    Article  CAS  PubMed  Google Scholar 

  9. Choi YW, Kotzin B, Herron L, Callahan J, Marrack P, Kappler J . Interaction of Staphylococcus aureus toxin ‘superantigens’ with human T cells. Proc Natl Acad Sci USA 1989; 86: 8941–8945.

    Article  CAS  PubMed  Google Scholar 

  10. Konno A, Okada K, Mizuno K, Nishida M, Nagaoki S, Toma T et al. CD8alpha alpha memory effector T cells descend directly from clonally expanded CD8alpha +beta high TCRalpha beta T cells in vivo. Blood 2002; 100: 4090–4097.

    Article  CAS  PubMed  Google Scholar 

  11. Gladman DD, Ibanez D, Urowitz MB . Systemic lupus erythematosus disease activity index 2000. J Rheumatol 2002; 29: 288–291.

    Google Scholar 

  12. Sullivan KM, Muraro P, Tyndall A . Hematopoietic cell transplantation for autoimmune disease: updates from Europe and the United States. Biol Blood Marrow Transplant 2010; 16: S48–S56.

    Article  PubMed  Google Scholar 

  13. Hugle T, Daikeler T . Stem cell transplantation for autoimmune diseases. Haematologica 2010; 95: 185–188.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Roord ST, de Jager W, Boon L, Wulffraat N, Martens A, Prakken B et al. Autologous bone marrow transplantation in autoimmune arthritis restores immune homeostasis through CD4+CD25+Foxp3+ regulatory T cells. Blood 2008; 111: 5233–5241.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Y Kanda.

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Wada, H., Terasako, K., Kamiya, Y. et al. Immune recovery after autologous PBSC transplantation without in vitro graft manipulation for refractory systemic lupus erythematosus. Bone Marrow Transplant 46, 1450–1454 (2011). https://doi.org/10.1038/bmt.2010.332

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