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

Abstract

The importance of anti‐HLA antibodies in transplantation settings, such as HLA‐mismatched or haploidentical hematopoietic stem cell transplantation and platelet refractoriness, is widely recognized. In previous reports, it was mentioned that several cut‐off values of donor‐specific anti‐HLA antibodies mean fluorescence intensity (MFI) were related to graft rejection in the environment of HLA mismatched stem cell transplantation and the aim of this study was to investigate the prevalence and risk factors of anti‐HLA antibodies according to those cut‐off values of MFI. A total of 3805 patients with hematologic disease were prospectively enrolled and analyzed. When using MFI of anti‐HLA antibodies ≥500, ≥1000, ≥1500, ≥2000, ≥5000, and ≥ 10,000 as cut‐off values for positivity, the prevalence of class I or II anti‐HLA antibodies ranged from 4.6% to 20.2% in all cases. When the MFI cut‐off value was ≥500 for positivity, multivariate analysis indicated that platelet transfusion, underlying disease, and pregnancy were the most important risk factors for the presence of anti‐HLA antibodies for the total patients. Subgroup analysis according to age, gender, and underlying disease showed that pregnancy was the most important risk factor for the presence of anti‐HLA antibodies. For all patients (n = 3805), when anti‐HLA antibody positivity was defined according to different MFI cut‐off values, including ≥1000, ≥1500, ≥2000, ≥5000, and ≥ 10,000, an association of platelet transfusion and pregnancy with anti‐HLA antibodies was also demonstrated. Our results suggest that pregnancy and platelet transfusion are the main risk factors for the prevalence of anti‐HLA antibodies in haploid allograft candidates, providing evidence for guiding the evaluation of anti‐HLA antibodies and helping donor selection for HLA‐mismatched transplant candidates.

Platelet transfusions in haploidentical haematopoietic stem cell allograft candidates: Protecting HLA‐A and HLA‐B antigens through eplet analysis

“…Transfusions with related-donor platelets have better haemostasis and a lower likelihood of bleedingespecially if the three HLA-A, -B, and -C loci are identical. 3 Factors other than eplet-or antigen mismatch also have a role in immunization after platelet transfusion. Indeed, the results of a recent study in a mouse model showed that chemotherapy led to enhanced alloantibody responses to allogeneic platelet transfusion.…”

“…1,2 In a cohort of 3805 patients with haematologic disease, the prevalence of class I or II anti-HLA antibodies ranged from 4.6% to 20.2% (depending on the cut-off value for positivity used). 3 HLA antibodies can be formed through the activation of HLA-specific humoral immune mechanisms, in several ways; the main settings include pregnancy, blood transfusion (especially platelet transfusion), and previous organ transplantation. In patients with haematologic disease, the presence of anti-HLA DSAs (defined according to various mean fluorescence intensity (MFI) cut-off values, ranging from 1000 to 10,000) was associated with platelet transfusion and pregnancy.…”

“…In patients with haematologic disease, the presence of anti-HLA DSAs (defined according to various mean fluorescence intensity (MFI) cut-off values, ranging from 1000 to 10,000) was associated with platelet transfusion and pregnancy. 3 Given that platelet transfusion is the main risk factor for the emergence of anti-HLA class I antibodies in haploidentical allograft candidates, the assessment of these antibodies can help to avoid platelet-transfusion refractoriness. 4 Moreover, this information about anti-HLA antibodies is useful for donor selection for HLAmismatched transplant candidates.…”

“…It is well known that the presence of DSAs prior to mismatched and/or haploidentical allogeneic HSCT is associated with poor primary engraftment and graft survival 1,2 . In a cohort of 3805 patients with haematologic disease, the prevalence of class I or II anti‐HLA antibodies ranged from 4.6% to 20.2% (depending on the cut‐off value for positivity used) 3 . HLA antibodies can be formed through the activation of HLA‐specific humoral immune mechanisms, in several ways; the main settings include pregnancy, blood transfusion (especially platelet transfusion), and previous organ transplantation.…”

“…HLA antibodies can be formed through the activation of HLA‐specific humoral immune mechanisms, in several ways; the main settings include pregnancy, blood transfusion (especially platelet transfusion), and previous organ transplantation. In patients with haematologic disease, the presence of anti‐HLA DSAs (defined according to various mean fluorescence intensity (MFI) cut‐off values, ranging from 1000 to 10,000) was associated with platelet transfusion and pregnancy 3 . Given that platelet transfusion is the main risk factor for the emergence of anti‐HLA class I antibodies in haploidentical allograft candidates, the assessment of these antibodies can help to avoid platelet‐transfusion refractoriness 4 .…”