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

Elayeb, Rahma; Tamagne, Marie; Bierling, Philippe; Noizat‐Pirenne, F.; Vingert, Benoît

doi:10.3324/haematol.2015.134171

Cited by 15 publications

(28 citation statements)

References 53 publications

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“…Multiple studies have established that certain inflammatory disorders and inflammatory stimuli increase the frequency and magnitude of alloimmune responses to RBC Ags (12–16, 19–21). However, the molecular mechanisms underlying these findings have not been previously studied.…”

Section: Discussionmentioning

confidence: 99%

“…These findings agree with prior studies demonstrating a critical role for cDC activation in T cell—dependent alloimmune responses to stored RBCs expressing the HOD Ag (18, 63). A recent study reported that the timing of poly(I:C) treatment influences alloantibody responses to transfused HOD RBCs (19). However, in contrast to our findings, the anti-HEL alloimmune response of mice treated with poly(I:C) 7 d prior to HOD RBC transfusion was significantly higher than those treated just 4 h prior to transfusion.…”

Section: Discussionmentioning

confidence: 99%

“…Given the large number of antigenic differences between human donors and recipients, multiple groups have used murine transfusions models that allow examination of alloimmune responses to a single donor RBC Ag (19–21). In the absence of an adjuvant, transfusion of mouse RBCs expressing human or model RBC Ags results in low-level alloimmune responses in some donor models and no response in others.…”

mentioning

confidence: 99%

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Type I IFN Is Necessary and Sufficient for Inflammation-Induced Red Blood Cell Alloimmunization in Mice

Gibb

Liu

Natarajan

et al. 2017

The Journal of Immunology

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During RBC transfusion, production of alloantibodies against RBC non-ABO Ags can cause hemolytic transfusion reactions and limit availability of compatible blood products, resulting in anemia-associated morbidity and mortality. Multiple studies have established that certain inflammatory disorders and inflammatory stimuli promote alloimmune responses to RBC Ags. However, the molecular mechanisms underlying these findings are poorly understood. Type I IFNs (IFN-α/β) are induced in inflammatory conditions associated with increased alloimmunization. By developing a new transgenic murine model, we demonstrate that signaling through the IFN-α/β receptor is required for inflammation-induced alloimmunization. Additionally, mitochondrial antiviral signaling protein—mediated signaling through cytosolic pattern recognition receptors was required for polyinosinic-polycytidylic acid—induced IFN-α/β production and alloimmunization. We further report that IFN-α, in the absence of an adjuvant, is sufficient to induce RBC alloimmunization. These findings raise the possibility that patients with IFN-α/β—mediated conditions, including autoimmunity and viral infections, may have an increased risk of RBC alloimmunization and may benefit from personalized transfusion protocols and/or targeted therapies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Type I IFN Is Necessary and Sufficient for Inflammation-Induced Red Blood Cell Alloimmunization in Mice

Gibb

Liu

Natarajan

et al. 2017

The Journal of Immunology

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“…It is currently unknown if TLRs are involved in alloimmunization in humans. Nonetheless, it is well documented that stimulation of certain TLRs promotes alloimmunization in mouse models (Hendrickson et al, 2006;Yu et al, 2007;Hendrickson et al, 2008;Elayeb et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Identification of genetic biomarkers for alloimmunization in sickle cell disease

et al. 2019

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Summary Most sickle cell disease (SCD) patients rely on blood transfusion as their main treatment strategy. However, frequent blood transfusion poses the risk of alloimmunization. On average, 30% of SCD patients will alloimmunize while other patient groups form antibodies less frequently. Identification of genetic markers may help to predict which patients are at risk to form alloantibodies. The aim of this study was to evaluate whether genetic variations in the Toll‐like receptor pathway or in genes previously associated with antibody‐mediated conditions are associated with red blood cell (RBC) alloimmunization in a cohort of SCD patients. In this case‐control study, cases had a documented history of alloimmunization while controls had received ≥20 RBC units without alloantibody formation. We used a customized single nucleotide polymorphism (SNP) panel to genotype 690 SNPs in 275 (130 controls, 145 cases) patients. Frequencies were compared using multiple logistic regression analysis. In our primary analysis, no SNPs were found to be significantly associated with alloimmunization after correction for multiple testing. However, in a secondary analysis with a less stringent threshold for significance we found 19 moderately associated SNPs. Among others, SNPs in TLR1/TANK and MALT1 were associated with a higher alloimmunization risk, while SNPs in STAM/IFNAR1 and STAT4 conferred a lower alloimmunization risk.

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“…Mouse models of alloimmunization have provided insight into the immune mechanisms inducing alloimmunization. The stimulation of TLRs increases the frequency and magnitude of alloantibody production mediated by splenic dendritic cells and CD4 + T cells in different blood group systems (9)(10)(11)(12)(13)(14)(15).…”

mentioning

confidence: 99%

Anti-CD20 Antibody Prevents Red Blood Cell Alloimmunization in a Mouse Model

Elayeb

Tamagne

Pinheiro

et al. 2017

The Journal of Immunology

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Alloimmunization against RBCs can cause life-threatening delayed hemolytic transfusion reactions. Anti-CD20 Ab has recently been used to prevent alloimmunization. However, its effects remain unclear, particularly in lymphoid organs. We investigated the impact of murine anti-CD20 Ab in the blood and spleen. We assessed protocols for preventing primary alloimmunization and for abolishing established alloimmunization. Prophylactic protocols prevented alloimmunization. However, anti-CD20 treatment could only limit the further amplification of established alloimmunization. Residual B cell subtype distribution was disrupted in the spleen, but adoptive transfer studies indicated that these cells were neither plasma nor memory cells. Anti-CD20 Ab had a major effect on alloreactive CD4 T cells, increasing the expansion of this population and its CD40 expression, while lowering its CD134 expression, thereby confirming its role in alloimmunization. In conclusion, this study shows that anti-CD20 immunotherapy can prevent RBC Ab development. However, this immunotherapy is limited by the increase in alloreactive CD4 T lymphocytes. Nevertheless, treatment with anti-CD20 Abs should be considered for patients requiring transfusion with a very high risk of alloimmunization and life-threatening complications.

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

Cited by 15 publications

References 53 publications

Type I IFN Is Necessary and Sufficient for Inflammation-Induced Red Blood Cell Alloimmunization in Mice

Type I IFN Is Necessary and Sufficient for Inflammation-Induced Red Blood Cell Alloimmunization in Mice

Identification of genetic biomarkers for alloimmunization in sickle cell disease

Anti-CD20 Antibody Prevents Red Blood Cell Alloimmunization in a Mouse Model

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