Autoimmunity Following Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

Autoimmune manifestations after allogeneic hematopoietic stem cell transplantation (AHSCT) are rare and poorly understood due to the complex interplay between the reconstituting immune system and transplant-associated factors. While autoimmune manifestations following AHSCT have been observed in children with graft-versus-host disease (GvHD), an alloimmune process, they are distinct from the latter in that they are generally restricted to the hematopoietic compartment, i.e., autoimmune hemolytic anemia, thrombocytopenia, and/or neutropenia. Autoimmune cytopenias in the setting of ASHCT represent a donor against donor immune reaction. Non-hematologic autoimmune conditions in the post-AHSCT setting have been described and do not currently fall under the GvHD diagnostic criteria, but could represent alloimmunity since they arise from the donor immune attack on the antigens that are shared by the donor and host in the thyroid, peripheral and central nervous systems, integument, liver, and kidney. As in the non-transplant setting, autoimmune conditions are primarily antibody mediated. In this article we review the incidence, risk factors, potential pathophysiology, treatment, and prognosis of hematologic and non-hematologic autoimmune manifestations in children after AHSCT.

Keywords: allogeneic; alloimmunity; autoimmune cytopenia; autoimmune hemolytic anemia; autoimmunity; hematopoietic stem cell transplantation; immune reconstitution; non-hematologic.

FIGURE 1

Biological and clinical features of autoimmune manifestations following AHSCT. (A) Proposed pathophysiology for the development of autoimmune manifestations after AHSCT as a result of donor T regulatory (T reg) cell impairment. (B) Donor immune reactions directed against donor red blood cell (RBC) antigens mediate autoimmune hemolytic anemia after AHSCT. (C) GvHD versus “autoimmune” non-hematologic tissue/organ targets outlined in red and blue, respectively.