Red blood cell alloimmunization in sickle cell disease: pathophysiology, risk factors, and transfusion management

Yazdanbakhsh, Karina; Ware, Russell E.; Noizat‐Pirenne, F.

doi:10.1182/blood-2011-11-327361

Cited by 332 publications

(394 citation statements)

References 114 publications

Supporting

Mentioning

369

Contrasting

Unclassified

Order By: Relevance

“…This susceptibility for alloimmunization in SCD has previously been explained by the antigenic differences between donors and recipients, SCD specific factors such as chronic inflammation and patient-related factors such as genetic background [2]. Our comparison does have its limitations as these cohorts were not fully comparable.…”

Section: Discussionmentioning

confidence: 61%

Early occurrence of red blood cell alloimmunization in patients with sickle cell disease

et al. 2016

View full text Add to dashboard Cite

Red blood cell (RBC) alloimmunization is a major complication of transfusion therapy in sickle cell disease (SCD). Identification of high-risk patients is hampered by lack of studies that take the cumulative transfusion exposure into account. In this retrospective cohort study among previously non-transfused SCD patients in the Netherlands, we aimed to elucidate the association between the cumulative transfusion exposure, first alloimmunization and independent risk factors. A total of 245 patients received 11 952 RBC units. Alloimmunization occurred in 43 patients (18%), half of them formed their first alloantibody before the 8th unit. In patients with exposure to non-extended matched transfusions (ABO and RhD) the cumulative alloimmunization risk increased up to 35% after 60 transfused units. This was significantly higher compared to a general transfused population (HR 6.6, CI 4.2-10.6). Receiving the first transfusion after the age of 5 was an independent risk factor for alloimmunization (HR 2.3, CI 1.0-5.1). Incidental, episodic transfusions in comparison to chronic scheme transfusions (HR 2.3, CI 0.9-6.0), and exposure to non-extended matched units in comparison to extended matching (HR 2.0, CI 0.9-4.6) seemed to confer a higher alloimmunization risk. The majority of first alloantibodies are formed after minor transfusion exposure, substantiating suggestions of a responder phenotype in SCD and stressing the need for risk factor identification. In this study, older age at first transfusion, episodic transfusions and non-extended matched transfusions appeared to be risk factors for alloimmunization.

show abstract

Section: Discussionmentioning

confidence: 61%

Early occurrence of red blood cell alloimmunization in patients with sickle cell disease

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Despite its therapeutic benefits, 20-60% patients with SCD develop alloantibodies with specificities against disparate antigens on transfused red blood cells, causing complications ranging from life-threatening hemolytic transfusion reactions, to logistical problems in finding compatible red cells for transfusion. 13 Given their key role in providing help to B cells and driving antibody responses, T FH cells are likely to be critical in alloimmunization biology. In a recent study of a cohort of transfused patients with SCD studied by Vingert et al, 14 despite a higher frequency of T FH cells in non-alloimmunized patients, only the alloimmunized group displayed antigenspecific T FH cells expressing IL-21, suggesting that T FH cells may play a role in alloimmunization.…”

Section: T Follicular Helper (T Fh ) Cells Have Emerged As the Main Ementioning

confidence: 99%

TIGIT-positive circulating follicular helper T cells display robust B-cell help functions: potential role in sickle cell alloimmunization

et al. 2015

View full text Add to dashboard Cite

© F e r r a t a S t o r t i F o u n d a t i o nphoid T FH , cT FH cells can express significant levels of surface programmed cell death-1 (PD-1), 31 although the function of PD-1 on T FH cells remains controversial since it is associated with both promotion 16,17 and inhibition of B-cell responses. 18,[32][33][34] Taken together, these reports underscore the need for better characterization of markers for cT FH cells displaying defined functions not only in steady state but also in diseases. Remarkably, PD-1 has been described as a member of the growing family of inhibitory receptors also referred to as immune checkpoints, responsible for aborting T-cell responses. 35 Interestingly, another member of the immune checkpoint family, TIGIT (T-cell immunoreceptor with Ig and immunoreceptor tyrosinebased inhibitory domains), was reported to be overexpressed on both tonsillar and cT FH cells, 17 and was shown to be involved in interactions between T cells and follicular dendritic cells to regulate B-cell responses. 36,37 However, the functional activity of TIGIT on T FH cells, including cT FH cells, has not been studied to date.In this study, we took the approach of using TIGIT and PD-1 to characterize the phenotype and function of circulating T FH subsets and to investigate whether expression of these molecules on cT FH cells modulated their functions in healthy volunteer donors and in a group of chronically transfused SCD patients with or without alloantibodies. Methods Human samplesAll studies were approved by the Institutional Review Boards of the New York Blood Center (NYBC). De-identified fresh leukopaks were obtained from healthy donors at the NYBC. For SCD patients' samples, blood was obtained solely from discard apheresis waste bags obtained during erythrocytapheresis procedures at the Children's Hospital of Philadelphia (see Online Supplementary Material for details). T-cell studiesFreshly-sorted CD4 + T-cell subsets and autologous naïve or memory B cells were used (see Online Supplementary Material for details). Blocking antibodies for TIGIT 38 and PD-1 34,39 were preincubated with sorted T cells before being co-cultured with autologous B cells. Results PD- Expression of ICOS, CD40L and IL-21 by TIGIT + cT FH cellsWe next tested whether TIGIT + cT FH cells were functionally different from cT FH + cT FH populations from a small number of healthy donors (n=3 or 4) were sorted and their ability to express T FH -associated co-stimulatory markers and cytokines following stimulation was compared to those of sorted autologous PD-1 -/TIGIT -subsets (gating strategy shown in Online Supplementary Figure S1). As a control, sort-purified autologous CXCR5 -non-cT FH cells expressing TIGIT E. Godefroy et al. 1416haematologica | 2015; 100(11) A B C© F e r r a t a S t o r t i F o u n d a t i o n ("TIGIT+") or not ("TIGIT-") were also tested. We first monitored expression of co-stimulatory molecules CD40L and ICOS, both specialized in providing Bcell help, on T-cell subsets before or after stimulation by immunos...

show abstract

“…2 In humans, several genotypes of class II major histocompatibility complex (MHC II) could be implicated in alloimmunization against specific antigens but controversy remains regarding this. 3,4 Little is known about the role of CD4 + T cells in alloimmunization, 5 except for Treg cells.…”

Section: Introductionmentioning

confidence: 99%

Red blood cell alloimmunization is influenced by the delay between Toll-like receptor agonist injection and transfusion

et al. 2015

View full text Add to dashboard Cite

Red blood cell alloimmunization in sickle cell disease: pathophysiology, risk factors, and transfusion management

Cited by 332 publications

References 114 publications

Early occurrence of red blood cell alloimmunization in patients with sickle cell disease

Early occurrence of red blood cell alloimmunization in patients with sickle cell disease

TIGIT-positive circulating follicular helper T cells display robust B-cell help functions: potential role in sickle cell alloimmunization

Red blood cell alloimmunization is influenced by the delay between Toll-like receptor agonist injection and transfusion

Contact Info

Product

Resources

About