Prevalence and risk factors of having antibodies to class I and II human leukocyte antigens in older haploidentical allograft candidates

Abstract

The effect of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) has been recognized as a factor in graft failure (GF) in patients who underwent umbilical cord blood transplantation (UBT), matched unrelated donor transplantation (MUDT), or haploidentical stem cell transplantation (haplo-SCT). Presently, we know little about the prevalence of and risk factors for having anti-HLA antibodies among older transplant candidates. Therefore, we analyzed 273 older patients with hematologic disease who were waiting for haplo-SCT. Among all patients, 73 (26.7%) patients had a positive panelreactive antibody (PRA) result for class I, 38 (13.9%) for class II, and 32 (11.7%) for both. Multivariate analysis showed that females were at a higher risk for having a PRA result for class II (P = 0.001) and for having antibodies against HLA-C and HLA-DQ. Prior pregnancy was a risk factor for having a PRA result for class I (P < 0.001) and for having antibodies against HLA-A, HLA-B and HLA-DQ. Platelet transfusions were risk factors for the following: having a positive PRA result for class I (P = 0.014) and class II (P < 0.001); having antibodies against HLA-A, HLA-B, HLA-C, HLA-DP, HLA-DQ, and HLA-DR; and having higher mean fluorescence intensity (MFI) of PRA for class I (P = 0.042). In addition, previous total transfusions were at high risk for having higher numbers of antibodies to specific HLA loci (P = 0.005), and disease course (7.5 months or more) (P = 0.020) were related to higher MFI of PRAs for class I. Our findings indicated that female sex, prior pregnancy, platelet transfusions and disease courses are independent risk factors for older patients with hematologic disease for having anti-HLA antibodies, which could guide anti-HLA antibody monitoring and be helpful for donor selection. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is recognized as an effective therapy for the majority of malignant hematologic diseases 1-4. However, primary and secondary graft failure (GF) remain a serious complication of allo-HSCT. Multiple factors have been implicated in GF, such as the primary diagnosis, advanced disease status, conditioning regimens, and stem cell dose 5-8. In recent years, the effects of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) have been recognized as a factor in GF 9-11 , either in patients who underwent umbilical cord blood transplantation (UBT), matched unrelated donor transplantation (MUDT), or haploidentical stem cell transplantation (haplo-SCT) 10-16. Therefore, DSAs can influence who is the best donor in HLA-mismatched allo-HSCT settings 17,18. Given the importance of anti-HLA antibodies, there have been many studies focusing on the prevalence and risk factors that may lead to the development of anti-HLA antibodies. Hung et al. 19 found that pregnancy and recent transfusion are independent risk factors for HLA sensitization in patients with end-stage renal disease. Akgul et al. 20 showed that in patients who are waiting for kidney transplantation, sensitiz...

Prevalence and risk factors of antibodies to HLA according to different cut‐off values of mean fluorescence intensity in haploidentical allograft candidates: A prospective study of 3805 subjects

“…Regardless of the MFI cut-off value of anti-HLA antibodies as ≥500, ≥1000, ≥1500, ≥2000, ≥5000, or ≥ 10,000, transfusion and pregnancy were the two most important risk factors for anti-HLA antibodies, as previously described. 2,13,14,18,[21][22][23] In our study, the reason for the different effects of RBC transfusion and platelet transfusion on anti-HLA antibody production may be that RBCs express low levels of HLA class I molecules (100-2000 per cell), whereas platelets are rich in HLA molecules. 34,35 This supports our finding that platelet transfusion, but not RBC transfusion, is a more important risk factor for the production of anti-HLA antibodies.…”

“…In addition, anti‐HLA antibody specificities were determined by LABScreen Single Antigen beads assay (One Lambda). Each step was performed in accordance with the manufacturer's instructions, as previously reported 22–24 . The MFI of anti‐HLA antibodies was calculated from the results after normalization to the negative control.…”

“…However, in the reports using similar experimental methods with our center, 500 is the most commonly used MFI cut-off value. 6,14,[21][22][23][25][26][27][28][29] In addition, several cutoff values also have been defined regarding the association of DSAs with graft rejection in HLA-mismatched stem cell transplant settings. A DSA MFI >1000 was associated with double-cord transplant engraftment failure.…”

“…Previous studies have demonstrated that the prevalence of anti-HLA antibodies ranges from <1% to 5% in healthy volunteers, [13][14][15] 24.4% to 54.4% in women after pregnancy, 12,16,17 23.2% to 32.8% in organ transplant candidates, [18][19][20] and 19.6% to 39.4% in HLA-mismatched SCT candidates. 3,4,6,9,[21][22][23][24] In addition, a study on platelet refractoriness also noted that 13% of refractory cases were caused by HLA allogeneic immunity. 11 The risk factors for HLA antibodies include prior pregnancy, blood transfusion, and previous transplantation.…”

Various approaches for accessing the influence of human leukocyte antigens disparity in haploidentical stem cell transplantation

“…42,43 This disparity in the presence of anti-HLA antibodies between our study and other studies might be a result of the differences in age, gender, type of disease, the number of transfusions, as well as the number of previous pregnancies. [42][43][44] The cross-match by CDC procedure was performed for all our patients and it was negative in 98.3% cases, the only exception was one female patient who had positive CM but also a high level of DSA (MFI 15 000). Because there were no other available donors for this patient, the decision was to proceed with the desensitization protocol prior to HSCT.…”