Dębska-Zielkowska Joanna, Słomiński Bartosz, Zielińska Hanna, Dukat-Mazurek Anna, Moszkowska Grażyna, Bieniaszewska Maria, Zaucha Jan Maciej, Trzonkowski Piotr, Zieliński Maciej
Department of Medical Immunology, Medical University of Gdańsk, Gdańsk, Poland.
Department of Hematology and Transplantology, Medical University of Gdańsk, Gdańsk, Poland.
Transpl Immunol. 2025 Sep;92:102274. doi: 10.1016/j.trim.2025.102274. Epub 2025 Aug 5.
Natural killer (NK) cells express killer immunoglobulin-like receptors (KIRs), which regulate their functions. Self-human leukocyte antigens (HLA) class I molecules act as inhibitory molecules for KIRs, blocking the killing activity of NK cells. Since normal NK activity may affect the outcomes of hematopoietic stem cell transplantation (HSCT) or bone marrow transplantation (BMT) from their HLA-matched sibling donors, we investigated the interaction between KIRs and class I HLA presented on NK cells. Complications such as graft-versus-host disease (GvHD) or transplant rejection may result because of deficient expression of class I HLA ligand inhibitors in the transplant recipient.
We examined the effect of missing KIR ligands (MSL) and KIR haplotypes on GvHD development, relapses, death, infections, and cell recovery in HSCT patients. Our group included 59 patients [n = 24 with acute myeloid leukemia (AML), n = 12 with chronic myeloid leukemia (CML), n = 12 with myelodysplastic syndrome (MDS), and n = 11 with acute lymphoblastic leukemia (ALL)], who received HSCT/BMT from their sibling donors.
Our results showed that haplotype AA was more common than Bx in donors for patients with MDS and was associated with a higher incidence of chronic (c) GvHD (p = 0.003). In this group, we also observed a statistically significant relationship between the AA donor haplotype and absolute neutrophil count reconstruction of 0.5 G/l (0.5 × 10 cells/L) under 28 days (p = 0.03). Our results also showed an excellent correlation between KIR MSL values and cGvHD in AML patients (r = 0.9932).
Our results indicate that KIR/HLA class I analysis at the stage of selection of a related donor could have an impact on the results of hematological transplantation and possibly reduce complications.