Efficacy of rituximab for the treatment and prevention of autoimmunity in patients with Wiskott-Aldrich syndrome and X-linked thrombocytopenia

•We used rituximab to treat and prevent autoimmunity in five patients with WAS and XLT.•Three patients with autoimmunity were successfully treated with rituximab before RIC.•None of the five patients developed autoimmunity, although two had mixed chimerism.•Rituximab did not cause a delay in donor B cell reconstitution after allogeneic HSCT.•An aberrant B cell-intrinsic mechanism is the central cause of autoimmunity in WAS. Immunological dysfunction in multiple lineages of hematopoietic cells and mixed chimerism after allogeneic hematopoietic stem cell transplantation (HSCT) are associated with an increased risk of autoimmunity in patients with Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia (XLT). Here, we report the efficacy of rituximab against autoimmunity in five patients with WAS and XLT. One patient with systemic arthritis and vasculitis, and two patients with immune thrombocytopenia were successfully treated with rituximab before initiating reduced-intensity conditioning. Rituximab was also used in combination with conditioning to prevent autoimmunity by depleting the recipient B cells in the other two patients with XLT. None of the patients developed autoimmunity without delay in donor B cell reconstitution, even though two patients had stable mixed chimerism after HSCT. These results suggest that aberrant B cell-intrinsic mechanisms are a central cause of autoimmunity, and rituximab is an effective therapeutic option for autoimmunity in patients with WAS and XLT.