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New autoimmune diseases after autologous hematopoietic stem cell transplantation for multiple sclerosis

Abstract

Secondary autoimmune diseases (2ndADs), most frequently autoimmune cytopenias (AICs), were first described after allogeneic hematopoietic stem cell transplantation (HSCT) undertaken for malignant and hematological indications, occurred at a prevalence of ~5–6.5%, and were attributed to allogeneic immune imbalances in the context of graft versus host disease, viral infections, and chronic immunosuppression. Subsequently, 2ndADs were reported to complicate roughly 2–14% of autologous HSCTs performed for an autoimmune disease. Alemtuzumab in the conditioning regimen has been identified as a risk for development of 2ndADs after either allogeneic or autologous HSCT and is consistent with the high rates of 2ndADs when using alemtuzumab as monotherapy. Due to the significant consequences but variable incidence, depending on conditioning regimen, of 2ndADs and similarity in known immune reconstitution kinetics after autologous HSCT for autoimmune diseases and after alemtuzumab monotherapy, we propose that an imbalance between B and T lineage regeneration early after HSCT may underlie the pathogenesis of 2ndADs.

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Fig. 1: Schematic T and B cell immune reconstitution in months after autologous HSCT for autoimmune disease.

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Correspondence to Richard K. Burt.

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Professor John A Snowden declares honoraria for an advisory board from MEDAC, and as an IDMC member for a trial supported by Kiadis Pharma, all outside the submitted work. Professor Paolo A. Muraro reports no conflict of interest. He discloses travel support and speaker honoraria from unrestricted educational activities organized by Novartis, Bayer HealthCare, Bayer Pharma, Biogen Idec, Merck-Serono and Sanofi Aventis. He also discloses consulting to Magenta Therapeutics and Jasper Therapeutics. All the other authors have nothing to declare.

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Burt, R.K., Muraro, P.A., Farge, D. et al. New autoimmune diseases after autologous hematopoietic stem cell transplantation for multiple sclerosis. Bone Marrow Transplant 56, 1509–1517 (2021). https://doi.org/10.1038/s41409-021-01277-y

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