Immunophenotypic parameters and RBC alloimmunization in children with sickle cell disease on chronic transfusion

Abstract

Alloimmunization against red blood cell (RBC) antigens is a cause of morbidity and mortality in transfused patients with sickle cell disease (SCD). To investigate distinguishing characteristics of patients who develop RBC alloantibodies after transfusion (responders) versus those who do not (non-responders), a crosssectional study of 90 children with SCD on chronic RBC transfusion therapy at a single institution was conducted in which 18 immune parameters (including T and B cell subsets) were tested via flow cytometry, and medical records were reviewed. RBC alloimmunization was present in 26/90 (29%) patients, with anti-E, K, and C among the most commonly detected alloantibodies despite prophylactic matching for these antigens at the study institution. In addition, RBC autoantibodies had been detected in 18/26 (69%) of alloimmunized versus 7/64 (11%) of non-alloimmunized patients (P < 0.0001). Alloimmunized patients were significantly older (median 13.0 years vs. 10.7 years, P 5 0.010) and had more RBC unit exposures (median 148 U vs. 82 U, P 5 0.020) than non-alloimmunized patients. Sex, age at initiation of chronic transfusion, splenectomy, stroke, and transfusion outside of the study institution were not significantly associated with RBC alloimmunization. Alloimmunized patients had a significantly increased percentage of CD41 T memory cells compared to non-alloimmunized patients (57% vs. 49%, P 5 0.0047), with no other significant differences in immune cell subsets or laboratory values detected between these groups. Additional research of RBC alloimmunization is needed to optimize transfusion therapy and to develop strategies to prevent alloimmunization.

Risk factors for red blood cell alloimmunization in the Recipient Epidemiology and Donor Evaluation Study (REDS‐III) database

“…Recently, Ryder et al (2016) reported that 16% of primarily male alloimmunized patients treated at a Veterans Administration hospital had a chronic autoimmune disorder, compared to 8% of nonalloimmunized patients. Multiple studies have also described a close association between RBC alloantibodies and RBC autoantibodies (Dhawan et al, 2014;Nickel et al, 2015). Animal studies (Gibb et al, 2017a,b) suggest that a potential unifying hypothesis for the connection between some types of autoimmunity (Crow, 2014) and alloimmunization may involve type 1 interferon signalling.…”

Absence of the spleen and the occurrence of primary red cell alloimmunization in humans

“…2,3 Contrasting these animal studies, some observational studies in thalassemia patients suggested splenectomy to be associated with increased red cell alloimmunization, 4,5 while others did not find any association. 6,7 In the study herein, we assessed the association between the anatomic absence of the spleen and (transfusion-related) red cell alloantibody induction in our multicenter case-control Risk Factors for Alloimmunization to Red Blood Cell Transfusion (R-FACT) study cohort. This cohort includes 505 alloimmunized cases and 1,010 non-alloimmunized matched controls among a primarily Caucasian source population of 24,063 patients receiving their first and subsequent red cell transfusions between January 2005 and December 2013 at one of six participating hospitals in the Netherlands, as described earlier.…”

Leukoreduced red blood cell transfusions do not induce platelet glycoprotein antibodies in patients with sickle cell disease

“…Patients in the transfused group had received a median of 93 RBC units (range, 6-543 units); additional details about this group have been previously reported. 22 The prevalence of antibodies in the transfused versus never transfused groups was not significantly different for any of the studied platelet glycoprotein antigens ( Table 1). The standardized OD values for each platelet glycoprotein antigen also were not significantly different for the transfused versus never transfused groups (Fig.…”

“…Patients in the transfused group were more likely to have undergone splenectomy (27% vs. 0%; p = 0.004) and were less likely to be receiving hydroxyurea (8% vs. 46%; p < 0.0001). Patients in the transfused group had received a median of 93 RBC units (range, 6‐543 units); additional details about this group have been previously reported …”