HistocompatIbility Antigens (HLA) and Transplantation

Abstract

Inborn errors of immunity (IEI) are disorders that result from pathogenic variants of genes involved in the immune response. Mutations of these genes place the host at increased risk of infections, autoimmunity, hyperinflammation, and other manifestations of immune dysregulation. The majority of IEI affect leukocyte lineages derived from hematopoietic cells and hence hematopoietic stem cell transplant (HSCT) constitutes a curative approach for many IEI. However, it is important to distinguish IEI linked to thymic defects where HSCT is less preferred over thymic transplant. The decision for pursuing HSCT among patients with IEI is a complex process that requires (1) full understanding of the immunological diagnosis (e.g., severe combined immunodeficiency [SCID]), with preferably the genetic cause, (2) indication for HSCT (i.e., poor prognosis without intervention [e.g., SCID] or severe clinical manifestations [infection, autoimmunity, cancer]), availability of (3) proper donor, and (4) conditioning regimen with an acceptable risk/benefit ratio. Recently, morbidity and mortality during this process have remarkably decreased due to improvements in human leukocyte antigen (HLA) typing, an increase in the use of alternative donors, decreased toxicity related to conditioning regimens, and advances in graft manipulation techniques to prevent complications such as graft-versus-host disease (GVHD). The complexities associated with HSCT in IEI require personalized approach with an ongoing need for continued optimization, and thus a collaborative relationship between immunologists and transplant specialists is of high importance. Despite the improvement in outcomes, complications occur during transplant as well as in the short-term peri-transplant and in the long-term posttransplant periods. Patients may seek medical care from the practicing Allergist Immunologist decades after their HSCT and a basic assessment of the immune reconstitution may be needed to guide their care promptly. Besides tracking immune reconstitution and toxicities, quality of life survey is needed to capture integral assessment of the patient during their lifelong journey after transplant.