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  • Development and resolution of secondary autoimmunity after autologous haematopoietic stem cell transplantation for systemic lupus erythematosus: competition of plasma cells for survival niches?

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Development and resolution of secondary autoimmunity after autologous haematopoietic stem cell transplantation for systemic lupus erythematosus: competition of plasma cells for survival niches?
  1. Tobias Alexander1,2,
  2. Sandra Schneider1,2,
  3. Bimba Hoyer1,2,
  4. Qingyu Cheng1,2,
  5. Andreas Thiel2,3,
  6. Sabine Ziemer4,
  7. Gerd-Rüdiger Burmester1,
  8. Renate Arnold5,
  9. Andreas Radbruch2,
  10. Falk Hiepe1,2
  1. 1 Department of Medicine, Division of Rheumatology and Clinical Immunology, Charité – University Medicine Berlin, Berlin, Germany
  2. 2 German Rheumatism Research Center (DRFZ), Berlin, Germany
  3. 3 Regenerative Immunology and Aging, Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité – University Medicine Berlin, Berlin, Germany
  4. 4 Institute of Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Charité – University Medicine Berlin, Berlin, Germany
  5. 5 Medical Department, Division of Hematology, Oncology and Tumor Immunology, Charité – University Medicine Berlin, Berlin, Germany
  1. Correspondence to Dr Falk Hiepe, Department of Medicine, Division of Rheumatology and Clinical Immunology, Charité – University Medicine Berlin, Charitéplatz 1, Berlin 10117, Germany; falk.hiepe{at}charite.de

https://doi.org/10.1136/annrheumdis-2012-202729

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    Haematopoietic stem cell transplantation (HSCT) is an effective treatment for severe autoimmune diseases such as systemic lupus erythematosus (SLE).1 However, it is increasingly recognised that these patients have an added propensity to develop secondary autoimmune disorders.2 ,3

    Here, we report on a 21-year-old male patient who received a CD34-selected autologous HSCT following conditioning with antithymocyte-globulin and cyclophosphamide (CYC) after written informed consent for refractory, severe SLE with renal, haematological, mucocutaneous and musculoskeletal manifestations (SLEDAI 19).1 Clinical remission was achieved for SLE within 3 months after HSCT and anti-double-stranded DNA (anti-dsDNA) antibodies disappeared despite immunosuppressive drug withdrawal. Eight months after HSCT, the patient presented with spontaneous joint and skin bleeding and was diagnosed with factor VIII (FVIII) inhibitor haemophilia with an activated partial thromboplastin time >100 s, FVIII activity <1% and a FVIII inhibitor titre of 435 Bethesda units (figure 1A). At that time point, flow cytometric analyses revealed a drastic increase in B cell numbers, expansion of circulating plasmablasts and a predominance of CD45RO memory CD4 T cells with oligoclonal T cell receptor Vβ expression (table 1), but clinical and laboratory tests showed no evidence of lupus activity. FVIII haemophilia was refractory to methylprednisolone, plasmapheresis, intravenous immunoglobulin (IVIG), intravenous CYC, rituximab and extracorporeal …

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    Footnotes

    • Handling editor Tore K Kvien

    • Contributors TA, SS, BH, QC and SZ carried out most of the experiments; FH, RA, AT and AHR made substantial contributions to the conception and design of the study; TA, G-RB, RA and FH conducted the clinical trial; and TA, SS, AHR and FH wrote the manuscript. All authors read and approved the final manuscript.

    • Funding This work was supported by the Deutsche Forschungsgemeinschaft (SFB650 TP12 and TP17).

    • Competing interests None.

    • Patient consent Obtained.

    • Ethics approval Local IRB Berlin.

    • Provenance and peer review Not commissioned; externally peer reviewed.