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Prognostic role of KIR genes and HLA-C after hematopoietic stem cell transplantation in a patient cohort with acute myeloid leukemia from a consanguineous community

Bone Marrow Transplantation volume 53, pages 1170–1179 (2018)Cite this article

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Abstract

NK cell activity is tuned by a balance of activating and inhibitory signals transmitted via their respective receptors, including killer immunoglobulin-like receptors (KIRs). The impact of NK cells on graft-versus-leukemia following hematopoietic stem cell transplantation (HSCT) is well established. These effects sometimes lead to GvHD. The link between KIR/HLA interaction and GvHD remains unclear. Herein, we studied the impact of the KIR/HLA interaction on HSCT outcomes in a longitudinal follow-up study of a highly consanguineous HLA-matched related cohort. Peripheral blood DNA was collected from HSCT donor–recipient pairs (n = 87), including 41 AML pairs. KIR and HLA were genotyped and significant results were only measured when matching KIR (donor) with HLA (recipients). GvHD was observed in 47% of patients. KIR2DL1_C2 and 2DS2_C1 (P = 0.02 and 0.04, respectively) matching was associated with an increased incidence of acute GvHD in AML donor–recipient pairs. The rate of chronic GvHD also rose in AML patients who were matched for KIR2DS1_C2 (P = 0.004) and had either KIR2DL2 or KIR2DS2 (P = 0.03). In conclusion, matching of KIR2DL1, 2DS1, and 2DS2 in donors with their HLA-C ligands in recipients is associated with increased GvHD, and holds potential for selection of HSCT donors.

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Acknowledgements

The authors would like to thank Miss Reguia Belkhedim and her team for coordinating patient consent and sample collection. Prof. Hannu Turpeinen is kindly acknowledged for critically reviewing our manuscript. Finally, we would like to thank the HSCT recipients and donors for their participation in this study.

Funding:

This study was approved and funded by King Abdul-Aziz City for Science and Technology, Riyadh, Saudi Arabia, as part of grant number AT-26-03 and by RAC # 2051 001, King Faisal Specialist Hospital and Research Centre.

Author contributions:

AG: Conception and design, supervised laboratory investigations, interpretation/analysis and presentation of data and manuscript writing. AS: Performed KIR typing and preliminary analysis of immunogenetics data and participated in manuscript editing. AE: Performed statistical analysis. AI: Assisted AG and AS in performing HLA typing by high resolution, and contributed to data analysis. NC, SYM, SM, AH, MS, FA, RE, and SH: screened and followed up the patients and critically reviewed the manuscript. TE: assisted AE in statistical analysis, presentation of the data, and revising the manuscript critically for important intellectual content. RY: provided blood samples and clinical data. MA: participated in the study design, critically reviewed the manuscript for intellectual and clinical contents, and participated in manuscript editing. KA: Principal investigator seeks and obtained funds from KACST for the study, also conception, design, and final approval of manuscript.

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Author notes

  1. These authors contributed equally: Ameera Gaafar, Atia Sheereen.

Authors and Affiliations

  1. Stem Cell and Tissue Re-engineering Program, King Faisal Specialist Hospital and Research Centre, Riyadh, 11211, Saudi Arabia

    Ameera Gaafar, Atia Sheereen, Alia Iqneibi & Khalid Alhussein

  2. King Faisal Cancer Center, King Faisal Specialist Hospital and Research Centre, Riyadh, 11211, Saudi Arabia

    Fahad Almohareb, Naeem Chaudhri, Said Y. Mohamed, Amr Hanbali, Marwan Shaheen, Feras Alfraih, Riad El Fakih, Riad Youniss, Tusneem Elhassan, Shahrukh Hashmi & Mahmud Aljurf

  3. Department of Biostatistics, Epidemiology, and Scientific Computing, King Faisal Specialist Hospital and Research Centre, Riyadh, 11211, Saudi Arabia

    Abdelmoneim Eldali

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  1. Ameera Gaafar
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Correspondence to Ameera Gaafar or Khalid Alhussein.

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Gaafar, A., Sheereen, A., Almohareb, F. et al. Prognostic role of KIR genes and HLA-C after hematopoietic stem cell transplantation in a patient cohort with acute myeloid leukemia from a consanguineous community. Bone Marrow Transplant 53, 1170–1179 (2018). https://doi.org/10.1038/s41409-018-0123-7

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