Red blood cell alloimmunization is associated with lower expression of FcγR1 on monocyte subsets in patients with sickle cell disease

Balbuena‐Merle, Raisa; Curtis, Susanna A; Devine, Lesley; Gibb, David R.; Karafin, Matthew S.; Luckey, Chance John; Tormey, Christopher A.; Siddon, Alexa J.; Roberts, John D.; Hendrickson, Jeanne E.

doi:10.1111/trf.15463

Cited by 8 publications

(5 citation statements)

References 51 publications

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“…Given the role that monocytes play in immune responses, a recent study hypothesized that FcγR1 (CD64) expression on monocytes may be associated with RBC alloimmunization status in people with SCD. Contrary to the hypothesis, lower CD64 expression was observed on classical (CD64+CD14 high CD16 low ) and intermediate circulating monocytes (CD64+CD14 high CD16 high ) in alloimmunized people with SCD compared to non-alloimmunized people ( 80 ).…”

Section: Characteristic Of Cell Subsets As Related To Alloimmunizatiocontrasting

confidence: 76%

“…In addition, interleukin-6 receptor signaling has been shown to impact RBC alloimmunization in a murine model ( 103 ). Overall serum levels of multiple cytokines have not been correlated with a history of RBC alloimmunization in at least two studies of people with SCD ( 80 , 104 ); studies of serum cytokine profiles at the time of new antibody formation, though logistically difficult to coordinate, might be more informative.…”

Section: Characteristic Of Cell Subsets As Related To Alloimmunizatiomentioning

confidence: 99%

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Red blood cell alloimmunization and sickle cell disease: a narrative review on antibody induction

Hendrickson¹

2020

Ann Blood

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The high prevalence of red blood cell (RBC) alloantibodies in people with sickle cell disease (SCD) cannot be debated. Why people with SCD are so likely to form RBC alloantibodies, however, remains poorly understood. Over the past decade, a better understanding of non-ABO blood group antigen variants has emerged; RH genetic diversity and the role this diversity plays in RBC alloimmunization is discussed elsewhere. Outside of antigen variants, the immune systems of people with SCD are known to be different than those of people without SCD. Some of these differences are due to effects of free heme, whereas others are impacted by hyposplenism. Descriptive studies of differences in white blood cell (WBC) subsets, platelet counts and function, and complement activation between people with SCD and race-matched controls exist. Studies comparing the immune systems of alloimmunized people with SCD to non-alloimmunized people with SCD to race-matched controls without SCD have uncovered differences in T-cell subsets, monocytes, Fcγ receptor polymorphisms, and responses to free heme. Studies in murine models have documented the role that recipient inflammation plays in RBC alloantibody formation, with human studies reporting a similar association. Murine studies have also reported the importance of type 1 interferon (IFNα/β), known to play a pivotal role in autoimmunity, in RBC alloantibody formation. The goal of this manuscript is to review existing data on factors influencing RBC alloantibody induction in people with SCD with a focus on inflammation and other immune system considerations, from the bench to the bedside.

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Section: Characteristic Of Cell Subsets As Related To Alloimmunizatiocontrasting

confidence: 76%

Section: Characteristic Of Cell Subsets As Related To Alloimmunizatiomentioning

confidence: 99%

Red blood cell alloimmunization and sickle cell disease: a narrative review on antibody induction

Hendrickson¹

2020

Ann Blood

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“…Wnts secreted from monocytes may be important for preserving a functional cytoskeleton and maintaining the correct number of erythrocytes, which may be affected in monocytosis implicated in anemia and sickle cell disease. [104][105][106][107] Interestingly, in patients with sickle cell disease, RBC alloimmunization is associated with lower expression of specific monocyte markers, 108 and it is tempting to speculate that the secretion of Wnt from this monocyte subpopulation may be affected.…”

Section: Discussionmentioning

confidence: 99%

Circulating Wnt Ligands Activate the Wnt Signaling Pathway in Mature Erythrocytes

Siman-Tov

Zelikson

Caspi

et al. 2021

ATVB

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Objective: The deformation ability of erythrocytes is critical for their function and affects their mobility in the circulation. To circulate and travel through narrow vessels, erythrocytes must continuously alter their shape by modifying their cytoskeleton, which controls their elasticity and stability. Erythrocytes lack nuclei and other major organelles, and thus most of the known signaling cascades are thought to be inactive in these cells. As the noncanonical Wnt pathway affects cytoskeleton dynamics by posttranslational modifications, we hypothesized that this signaling pathway may affect erythrocytes. Approach and Results: We demonstrate that components of the noncanonical Wnt pathway are expressed in erythrocytes and that incubation of erythrocytes with Wnt ligands prolonged their survival both ex vivo, under storage conditions, and in posttransfusion recipient mice. We show that Wnt ligands modulate the erythrocyte cytoskeleton, enhancing its flexibility and strength. Importantly, we show that the noncanonical Wnt-5A ligand is secreted into the plasma and that monocytes and lymphocytes are a possible source of the Wnt effectors in the blood circulation. Conclusions: These findings provide evidence for intracellular signaling activity in enucleated cells and signal transduction in the blood circulation and thus open new and exciting avenues for studying the function of signaling pathways in the bloodstream.

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“…Additional studies identified a reduced number of PD1 + CXCR5 + circulating T follicular helper (Tfh) cells (including Tfh subsets) among alloimmunized compared with nonalloimmunized individuals ( 49 ). Further examination suggested that responders may also have lower expression of Fc gamma receptor type 1 (FcγR1) on classical and intermediate monocytes than nonresponders( 50 ).…”

Section: In Vitro Human Studies—the Responder–nonresponder Continuummentioning

confidence: 99%

The Development and Consequences of Red Blood Cell Alloimmunization

Arthur

Stowell

2023

Annu. Rev. Pathol. Mech. Dis.

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While red blood cell (RBC) transfusion is the most common medical intervention in hospitalized patients, as with any therapeutic, it is not without risk. Allogeneic RBC exposure can result in recipient alloimmunization, which can limit the availability of compatible RBCs for future transfusions and increase the risk of transfusion complications. Despite these challenges and the discovery of RBC alloantigens more than a century ago, relatively little has historically been known regarding the immune factors that regulate RBC alloantibody formation. Through recent epidemiological approaches, in vitro–based translational studies, and newly developed preclinical models, the processes that govern RBC alloimmunization have emerged as more complex and intriguing than previously appreciated. Although common alloimmunization mechanisms exist, distinct immune pathways can be engaged, depending on the target alloantigen involved. Despite this complexity, key themes are beginning to emerge that may provide promising approaches to not only actively prevent but also possibly alleviate the most severe complications of RBC alloimmunization. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 18 is January 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Red blood cell alloimmunization is associated with lower expression of FcγR1 on monocyte subsets in patients with sickle cell disease

Cited by 8 publications

References 51 publications

Red blood cell alloimmunization and sickle cell disease: a narrative review on antibody induction

Red blood cell alloimmunization and sickle cell disease: a narrative review on antibody induction

Circulating Wnt Ligands Activate the Wnt Signaling Pathway in Mature Erythrocytes

The Development and Consequences of Red Blood Cell Alloimmunization

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