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Class I and II human leukocyte antibodies in pediatric haploidentical allograft candidates: prevalence and risk factors

Abstract

Donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) were associated with graft failure (GF) following haploidentical stem cell transplantation (Haplo-HSCT). The prevalence and risk factors of DSAs in pediatric candidates remain to be determined. In a prospective trial (ChiCTR-OPC-15006672), 486 children with hematological diseases were enrolled to screen for the presence of anti-HLA class I and II antibodies of immunoglobulin G type. Fifty two patients (10.7%) demonstrated positive panel-reactive antibody (PRA) for class I; 24 (4.9%), for class II; and 13 (2.7%), for both. Multivariate analysis showed diagnosis was the independent risk factor for antibodies, as acute lymphoblastic leukemia (ALL) patients (HR0.141, 95% CI: 0.037–0.538, p = 0.004) had a lower incidence of class II PRAs and DSAs against HLA-B, DQ, and DR, whereas myelodysplastic syndrome (MDS) patients had a higher incidence of PRAs for both class I and class II (HR4.790, 95% CI: 1.010–22.716, p = 0.049), and DSAs against HLA-A, B, C, DP, and DQ. Older age (>12 vs. ≤12) was associated with DSAs against HLA-DP (HR0.194, 95% CI: 0.041–0.918, p = 0.039). Our findings provided novel evidence for prevalence and risk factors for PRAs and DSAs in pediatric candidates receiving haplo-HSCT, possibly benefiting anti-HLA antibody monitoring and donor selection.

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Acknowledgements

This work was supported by the National key research and development plan of China (2017YFA0104500), Foundation for Innovative Research Groups of the National Natural Science Foundation of China (Grant No. 81621001), National Natural Science Foundation of China (Grant No. 81870140, 81670166, 81873445, 81530046), Beijing Municipal Science & Technology Project (No. Z171100001017098 and Z18111000960000); the project of health collaborative innovation of Guangzhou city (no. 201704020214); Scientific Research Foundation for Capital Medicine Development(No. 2018-2-4084 and 2016-1-4082). We would also like to thank American Journal Experts (https://www.aje.com) for the assistance in editing this manuscript.

Authors contribution:

XYZ, XJH, YJC designed the study; ML, SZZ, and YJC collected the data; ML, SZZ, XJH, YJC, and XYZ analyzed the data and drafted the manuscript; and all authors contributed to data interpretation, manuscript preparation, and approved of the final version of the manuscript.

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Correspondence to Xiang-Yu Zhao.

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Lv, M., Zhai, SZ., Wang, Y. et al. Class I and II human leukocyte antibodies in pediatric haploidentical allograft candidates: prevalence and risk factors. Bone Marrow Transplant 54, 1287–1294 (2019). https://doi.org/10.1038/s41409-018-0427-7

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