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Mesenchymal stem cell transplantation for diffuse alveolar hemorrhage in SLE

Nature Reviews Rheumatology volume 6, pages 486–489 (2010)Cite this article

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Abstract

Background. A 19-year-old girl was diagnosed with systemic lupus erythematosus, based on findings of arthritis, malar rash, positive antinuclear antibody test and high levels of antibodies to double-stranded DNA. Two months after diagnosis, the patient presented with a sudden drop in blood hemoglobin level. Several days later, she developed bloody sputum, rapidly progressive dyspnea and hypoxemia. High-resolution CT showed diffuse alveolar infiltrates in both lung fields.

Investigations. Physical examination, complete blood count, erythrocyte sedimentation rate, urinalysis, 24-h urine protein excretion, fecal occult blood test, d-dimer test, acid hemolysis test, activated partial thromboplastin time and prothrombin time, direct and indirect Coombs tests, bone marrow smear, arterial blood gas, sputum smear and culture, and high-resolution CT scan of the chest.

Diagnosis. Diffuse alveolar hemorrhage associated with systemic lupus erythematosus.

Management. The patient did not respond to pulsed intravenous methylprednisolone (two courses of 500 mg per day for 3 days) and intravenous immunoglobulin (20 g per day for 5 days). The patient was referred to a specialist treatment center for allogenic transplantation using umbilical-cord-derived mesenchymal stem cells. She underwent transplantation with an infusion of 8 × 107 mesenchymal stem cells. After showing dramatic improvements in her clinical condition, oxygenation level, radiographic and hematological status, the patient was discharged from hospital approximately 5 weeks after undergoing transplantation.

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Figure 1: Chest HRCT scans before and after UC-MSCT.

References

  1. Santos-Ocampo, A. S., Mandell, B. F. & Fessler, B. J. Alveolar hemorrhage in systemic lupus erythematosus: presentation and management. Chest 118, 1083–1090 (2000).

    Article  CAS  Google Scholar 

  2. Zamora, M. R. et al. Diffuse alveolar hemorrhage and systemic lupus erythematosus. Medicine 76, 192–202 (1997).

    Article  CAS  Google Scholar 

  3. Guleria, R. & Pangtey, G. Lung in SLE. Indian Journal of Rheumatology 4, 131–132 (2007).

    Article  Google Scholar 

  4. Green, R. J. et al. Pulmonary capillaritis and alveolar hemorrhage. Chest 110, 1305–1316 (1996).

    Article  CAS  Google Scholar 

  5. Todd, D. J. & Costenbader, K. H. Dyspnoea in a young woman with active systemic lupus erythematosus. Lupus 18, 777–784 (2009).

    Article  Google Scholar 

  6. Cañas, C. et al. Diffuse alveolar hemorrhage in Colombian patients with systemic lupus erythematosus. Clin. Rheumatol. 26, 1947–1949 (2007).

    Article  Google Scholar 

  7. Chang, M. Y. et al. Diffuse alveolar hemorrhage in systemic lupus erythematosus: a single center retrospective study in Taiwan. Ren. Fail. 24, 791–802 (2002).

    Article  Google Scholar 

  8. Wu, C. Y. et al. Severe pulmonary hemorrhage as the initial presentation in systemic lupus erythematosus with active nephritis. Lupus 10, 879–882 (2001).

    Article  CAS  Google Scholar 

  9. Santos, B. H. et al. Pulmonary hemorrhage as a manifestation of systemic lupus erythematosus. Rev. Hosp. Clin. Fac. Med. S. Paulo 59, 47–50 (2004).

    Article  Google Scholar 

  10. Zhang, B. et al. Mesenchymal stem cells induce mature dendritic cells into a novel jagged-2-dependent regulatory dendritic cell population. Blood 113, 46–57 (2009).

    Article  CAS  Google Scholar 

  11. Nauta, A. J. & Fibbe, W. E. Immunomodulatory properties of mesenchymal stromal cells. Blood 15, 3499–3506 (2007).

    Article  Google Scholar 

  12. Prigione, I. et al. Reciprocal interactions between human mesenchymal stem cells and γδ T cells or invariant natural killer T cells. Stem Cells 27, 693–702 (2009).

    Article  CAS  Google Scholar 

  13. Sotiropoulou, P. A. et al. Interactions between human mesenchymal stem cells and natural killer cells. Stem Cells 24, 74–85 (2006).

    Google Scholar 

  14. Le Blanc, K. et al. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet 371, 1579–1586 (2008).

    Article  CAS  Google Scholar 

  15. Sun, L. Y. et al. Abnormality of bone marrow-derived stem cell in patients with systemic lupus erythematosus. Lupus 16, 121–128 (2007).

    Article  CAS  Google Scholar 

  16. Zhou, K. X. et al. Transplantation of human bone marrow mesenchymal stem cell ameliorates the autoimmune pathogenesis in MRL/lpr mice. Cell. Mol. Immunol. 5, 417–424 (2008).

    Article  Google Scholar 

  17. Sun, L. Y. et al. Mesenchymal stem cell transplantation reverses multi-organ dysfunction in systemic lupus erythematosus mice and humans. Stem Cells 27, 1421–1432 (2009).

    Article  CAS  Google Scholar 

  18. Zhao, F. et al. Therapeutic effects of bone marrow-derived mesenchymal stem cells engraftment on bleomycin-induced lung injury in rats. Transplant. Proc. 40, 1700–1705 (2008).

    Article  CAS  Google Scholar 

  19. Gupta, N. et al. Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice. J. Immunol. 179, 1855–1863 (2007).

    Article  CAS  Google Scholar 

  20. Weiss, M. L. & Troyer, D. L. Stem cells in the umbilical cord. Stem Cell Rev. 2, 155–162 (2006).

    Article  CAS  Google Scholar 

  21. Lu, L. L. et al. Isolation and characterization of human umbilical cord mesenchymal stem cells with hematopoiesis-supportive function and other potentials. Hematologica 91, 1017–1026 (2006).

    CAS  Google Scholar 

  22. Valencia, X. et al. Deficient CD4+CD25high T regulatory cell function in patients with active systemic lupus erythematosus. J. Immunol. 178, 2579–2588 (2007).

    Article  CAS  Google Scholar 

  23. Nalbandian, A., Crispín, J. C. & Tsokos, G. C. Interleukin-17 and systemic lupus erythematosus: current concepts. Clin. Exp. Immunol. 157, 209–215 (2009).

    Article  CAS  Google Scholar 

  24. Berger, M. J. et al. Differentiation of umbilical cord blood-derived multilineage progenitor cells into respiratory epithelial cells. Cytotherapy 8, 480–487 (2006).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors are grateful to the patient's family for granting permission to write this case report. They thank Dr. Xiang Hu and Shengqin Ye (Jiangsu Stem Cell Bank, Jiangsu, China) for providing the MSCs. They thank Dr. Gary S. Gilkeson (Department of Rheumatology, Medical University of South Carolina, Charleston, SC, USA) for his critical review of the manuscript. This work was supported by grants from the National Natural Science Foundation of China (No. 30772014 and No. 30972736), Jiangsu Province 135 Talent Foundation (RC2007002), Jiangsu Province Natural Science Foundation (No. 09KJB320010), Jiangsu Province Science-Technology Achievement Transforming Foundation (BA2009124), Jiangsu Province “Six Summit Talent” Foundation and Nanjing Health Bureau Young Scientists Launching Project (QYK09174).

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Authors and Affiliations

  1. Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, Jiangsu, China

    Jun Liang, Fei Gu, Hong Wang, Bingzhu Hua & Lingyun Sun

  2. Immunology Laboratory, Nanjing University Medical School, 22 Hankou Road, Nanjing, 210093, Jiangsu, China

    Yayi Hou

  3. Center for Craniofacial Molecular Biology, University of Southern California School of Dentistry, 2250 Alcazar Street, CSA 103, Los Angeles, 90033, CA, USA

    Songtao Shi

  4. Department of Pathology and Center of Infection and Immunology, The University of Hong Kong, Pokfulam Road, Hong Kong, China

    Liwei Lu

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  1. Jun Liang
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Correspondence to Lingyun Sun.

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Liang, J., Gu, F., Wang, H. et al. Mesenchymal stem cell transplantation for diffuse alveolar hemorrhage in SLE. Nat Rev Rheumatol 6, 486–489 (2010). https://doi.org/10.1038/nrrheum.2010.80

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