Are polymorphisms of the immunoregulatory factor CD40LG implicated in acute transfusion reactions?

Aloui, Chaker; Sut, Caroline; Prigent, Antoine; Fagan, Jocelyne; Cognasse, Fabrice; Granados-Herbepin, Viviana; Touraine, Renaud; Pozzetto, Bruno; Aouni, Mahjoub; Fendri, C.; Hassine, Mohsen; Chakroun, Tahar; Jemni-Yacoub, Saloua; Garraud, Olivier; Laradi, Sandrine

doi:10.1038/srep07239

Cited by 18 publications

(13 citation statements)

References 66 publications

(92 reference statements)

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“…CD40L gene polymorphism was found to influence the presentation of secreted CD40L (44). It has been hypothesized that this genetic characteristic of donors may affect pro-inflammatory secretion of donated platelets in BCs (45, 46). This type of result is plausible as well for other BRMs.…”

Section: Models Of Transfusion-associated Inflammation Hitmentioning

confidence: 99%

Transfusion as an Inflammation Hit: Knowns and Unknowns

et al. 2016

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Transfusion of blood cell components is frequent in the therapeutic arsenal; it is globally safe or even very safe. At present, residual clinical manifestations are principally inflammatory in nature. If some rare clinical hazards manifest as acute inflammation symptoms of various origin, most of them linked with conflicting and undesirable biological material accompanying the therapeutic component (infectious pathogen, pathogenic antibody, unwanted antigen, or allergen), the general feature is subtler and less visible, and essentially consists of alloimmunization or febrile non-hemolytic transfusion reaction. The present essay aims to present updates in hematology and immunology that help understand how, when, and why subclinical inflammation underlies alloimmunization and circumstances characteristic of red blood cells and – even more frequently – platelets that contribute inflammatory mediators. Modern transfusion medicine makes sustained efforts to limit such inflammatory hazards; efforts can be successful only if one has a clear view of each element’s role.

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Section: Models Of Transfusion-associated Inflammation Hitmentioning

confidence: 99%

Transfusion as an Inflammation Hit: Knowns and Unknowns

et al. 2016

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“…Il n'est pas aberrant d'imaginer que certains donneurs puissent être enclins à manifester eux-mêmes des symptomatologies super-inflammatoires dès lors que des circonstances extérieures (stimuli) seraient rencontrées (infection par exemple) : leurs cellules données -les plaquettes (et éven-tuellement les leucocytes résiduels) -ont-elles un seuil de déclenchement pro-inflammatoire supérieur à la moyenne des donneurs présentant des polymorphismes plus communs à ces molécules gouvernant l'inflammation ? Certains groupes de recherche -dont le nôtre -explorent cette piste parmi d'autres [61,62]. On pourra inclure dans ce chapitre également le terrain atopique (pro-allergique).…”

Section: Facteurs Possiblement Originaire Des Donneursunclassified

Transfusion et inflammation : hier – aujourd’hui – demain

Garraud

Hamzeh‐Cognasse

Laradi

et al. 2015

Transfusion Clinique et Biologique

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“…Thus, we hypothesized the existence of a genetic risk factor in relation to the donor. In an initial study, we investigated the coding sequences, exon-intron junctions and regulatory regions of CD40LG , but we did not find any particular genetic pattern of CD40LG in two groups of individuals regardless of whether their donated platelets induced an AE 16 , despite the fact that two CD40LG polymorphisms are involved in CD40LG regulation, namely, sequence variations in the 5′ UTR of CD40LG (rs3092952) 1 and a CA microsatellite in the 3′ UTR that affects mRNA stability 17 18 .…”

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Levels of human platelet-derived soluble CD40 ligand depend on haplotypes of CD40LG-CD40-ITGA2

Aloui

Prigent

Tariket

et al. 2016

Sci Rep

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Increased circulating soluble CD40 ligand (sCD40L) is commonly associated with inflammatory disorders. We aimed to investigate whether gene polymorphisms in CD40LG, CD40 and ITGA2 are associated with a propensity to secrete sCD40L; thus, we examined this issue at the level of human platelets, the principal source of sCD40L. We performed single polymorphism and haplotype analyses to test for the effect of twelve polymorphisms across the CD40LG, CD40 and ITGA2 genes in blood donors. ITGA2 presented a positive association with rs1126643, with a significant modification in sCD40L secretion (carriers of C allele, P = 0.02), unlike the investigated CD40LG and CD40 polymorphisms. One CD40LG haplotype (TGGC) showing rs975379 (C/T), rs3092952 (A/G), rs3092933 (A/G) and rs3092929 (A/C) was associated with increased sCD40L levels (1.906 μg/L (95% CI: 1.060 to 2.751); P = 0.000009). The sCD40L level was associated with the inter-chromosomal CD40LG/CD40/ITGA2 haplotype (ATC), displaying rs3092952 (A/G), rs1883832 (C/T) and rs1126643 (C/T), with increased sCD40L levels (P = 0.0135). Our results help to decipher the genetic role of CD40LG, CD40 and ITGA2 with regard to sCD40L levels found in platelet components. Given the crucial role of sCD40L, this haplotype study in a transfusion model may be helpful to further determine the role of haplotypes in inflammatory clinical settings.

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Are polymorphisms of the immunoregulatory factor CD40LG implicated in acute transfusion reactions?

Cited by 18 publications

References 66 publications

Transfusion as an Inflammation Hit: Knowns and Unknowns

Transfusion as an Inflammation Hit: Knowns and Unknowns

Transfusion et inflammation : hier – aujourd’hui – demain

Levels of human platelet-derived soluble CD40 ligand depend on haplotypes of CD40LG-CD40-ITGA2

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