Major Histocompatibility Complex and Hematopoietic Stem Cell Transplantation: Beyond the Classical HLA Polymorphism

Area of Science:

• Immunogenetics
• Transplantation immunology

Background:

• Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative therapy for hematological disorders.
• Donor selection relies on human leukocyte antigen (HLA) matching, but risks like disease relapse and graft-versus-host-disease persist.

Purpose of the Study:

• To explore the evolving criteria for selecting HSCT donors.
• To highlight the immunological role of HLA mismatches and Killer Immunoglobulin-like receptors (KIR) in transplant outcomes.

Main Methods:

• Review of current practices in HLA typing for HSCT donor selection.
• Analysis of the impact of HLA and KIR gene matching on transplant success and donor availability.

Main Results:

• Standard HLA matching (HLA-A, -B, -C, -DRB1, -DQB1) is crucial but insufficient to prevent all transplant complications.
• HLA mismatches can induce graft-versus-leukemia effects, potentially limiting disease recurrence in high-risk patients.
• Understanding KIR genes and permissible HLA mismatches expands the pool of suitable HLA-haploidentical and unrelated donors.

Conclusions:

• The definition of an ideal HSCT donor is dynamic, influenced by technological advancements and a deeper understanding of immunogenetics.
• Incorporating KIR genetics and permissible HLA mismatching strategies can enhance donor availability and improve HSCT outcomes.