Acquired Omenn-Like Syndrome, a Novel Posttransplant Autoaggression Syndrome Reversed by Rapamycin

Abstract

Graft-versus-host disease is uncommon in autologous hematopoietic cell transplantation (HCT) and is typically brief and mild. We report unusual, protracted, and severe Omenn syndrome-like autoaggression following autologous HCT. We identified a profound FOXP3 ؉ regulatory T cell defect that coincided with hyperinflammatory T cell responses which were reversible with rapamycin in vitro. CASE REPORT

Case Report: “Primary Immunodeficiency”—Severe Autoimmune Enteropathy in a Pediatric Heart Transplant Recipient Treated With Abatacept and Alemtuzumab

“…In Omenn syndrome, autoreactive T cells infiltrate the skin, GI tract, and other organs leading to erythroderma, chronic diarrhea, and failure to thrive ( 7 ). A similar phenomenon of autoreactive T cells has been recognized in some autologous HSCT recipients ( 8 , 9 ). Theoretically, patients undergoing autologous HCST should be exempt from GVHD, since there is no HLA disparity between infused stem cells and the recipient ( 9 ).…”

“…Autoimmune enteropathy has been described as a component of inborn errors of immunity such as immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) and other disorders with loss of T-cell tolerance, as well as in association with other non-syndromic immune-mediated conditions and as an isolated disorder ( 10 ). Autoimmune enteropathy is a well-recognized complication of GVHD in patients following allogeneic HSCT; however, recipients of autologous transplants can also have auto-GVHD and autoimmune enteropathy ( 8 , 9 ). Recent evidence suggests that in comparison to allogeneic GVHD driven by the disparity in donor and recipient HLA, the mechanism underlying autologous GVHD may be due to impaired reconstitution of the thymic medulla resulting in the loss of T-cell tolerance ( 11 , 12 ).…”

“…Theoretically, patients undergoing autologous HCST should be exempt from GVHD, since there is no HLA disparity between infused stem cells and the recipient ( 9 ). Interestingly, pathology similar to allogeneic GVHD is present in ~10% of autologous HCST recipients, termed “autologous GVHD” or “auto-GVHD,” but is typically mild and limited to the skin ( 8 ). However, a more severe presentation with gut involvement has been described, including patients with persistent diarrhea and GVHD-like pathology ( 9 ).…”