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

View Article: PubMed Central - PubMed

ABSTRACT

The CD40 ligand (CD40L/CD154), a member of TNF superfamily, is notably expressed on activated CD4+ T-cells and stimulated platelets. CD40L is linked to a variety of pathologies and to acute transfusion reactions (ATR). Mutations in this gene (CD40LG) lead to X-linked hyper-IgM syndrome. Some CD40LG polymorphisms are associated with variable protein expression. The rationale behind this study is that CD40L protein has been observed to be involved in ATR. We wondered whether genetic polymorphisms are implicated. We investigated genetic diversity in the CD40LG using DHPLC and capillary electrophoresis for screening and genotyping (n = 485 French and Tunisian blood donors). We identified significant difference in the CD40LG linkage pattern between the two populations. Variant minor alleles were significantly over-represented in Tunisian donors (P<0.0001 to 0.0270). We found higher heterogeneity in the Tunisian, including three novel low frequency variants. As there was not a particular pattern of CD40LG in single apheresis donors whose platelet components induced an ATR, we discuss how this information may be useful for future disease association studies on CD40LG.

No MeSH data available.


Frequency distribution of the number of (CA)n repeats in the CD40LG in the French (FR) and Tunisian (TN) populations.Allele frequencies correspond to the number of the group of test alleles divided by the total number of alleles.
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f3: Frequency distribution of the number of (CA)n repeats in the CD40LG in the French (FR) and Tunisian (TN) populations.Allele frequencies correspond to the number of the group of test alleles divided by the total number of alleles.

Mentions: Allele frequencies were calculated in the French and Tunisian donors and the data revealed no deviation from HWE; we had previously verified the different allele frequencies for (CA)n repeats between males and females (P = 0.297 and 0.137 for the French and the Tunisian donors, respectively). Twelve different alleles (from 18 to 31 CA repeats, corresponding to PCR products from 98 to 124 bp) were detected in the French cohort while 17 alleles (with 16 to 33 repeats, corresponding to PCR products from 94 to 128 bp) were observed in the Tunisian cohort. The (CA)26 allele was the central or median allele and the most represented one in both groups, albeit more frequent in French than in Tunisian donors (Figure 3).


Are polymorphisms of the immunoregulatory factor CD40LG implicated in acute transfusion reactions?
Frequency distribution of the number of (CA)n repeats in the CD40LG in the French (FR) and Tunisian (TN) populations.Allele frequencies correspond to the number of the group of test alleles divided by the total number of alleles.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5384113&req=5

f3: Frequency distribution of the number of (CA)n repeats in the CD40LG in the French (FR) and Tunisian (TN) populations.Allele frequencies correspond to the number of the group of test alleles divided by the total number of alleles.
Mentions: Allele frequencies were calculated in the French and Tunisian donors and the data revealed no deviation from HWE; we had previously verified the different allele frequencies for (CA)n repeats between males and females (P = 0.297 and 0.137 for the French and the Tunisian donors, respectively). Twelve different alleles (from 18 to 31 CA repeats, corresponding to PCR products from 98 to 124 bp) were detected in the French cohort while 17 alleles (with 16 to 33 repeats, corresponding to PCR products from 94 to 128 bp) were observed in the Tunisian cohort. The (CA)26 allele was the central or median allele and the most represented one in both groups, albeit more frequent in French than in Tunisian donors (Figure 3).

View Article: PubMed Central - PubMed

ABSTRACT

The CD40 ligand (CD40L/CD154), a member of TNF superfamily, is notably expressed on activated CD4+ T-cells and stimulated platelets. CD40L is linked to a variety of pathologies and to acute transfusion reactions (ATR). Mutations in this gene (CD40LG) lead to X-linked hyper-IgM syndrome. Some CD40LG polymorphisms are associated with variable protein expression. The rationale behind this study is that CD40L protein has been observed to be involved in ATR. We wondered whether genetic polymorphisms are implicated. We investigated genetic diversity in the CD40LG using DHPLC and capillary electrophoresis for screening and genotyping (n = 485 French and Tunisian blood donors). We identified significant difference in the CD40LG linkage pattern between the two populations. Variant minor alleles were significantly over-represented in Tunisian donors (P<0.0001 to 0.0270). We found higher heterogeneity in the Tunisian, including three novel low frequency variants. As there was not a particular pattern of CD40LG in single apheresis donors whose platelet components induced an ATR, we discuss how this information may be useful for future disease association studies on CD40LG.

No MeSH data available.