No Evidence that Knops Blood Group Polymorphisms Affect Complement Receptor 1 Clustering on Erythrocytes

Abstract

Clustering of Complement Receptor 1 (CR1) in the erythrocyte membrane is important for immune-complex transfer and clearance. CR1 contains the Knops blood group antigens, including the antithetical pairs Swain-Langley 1 and 2 (Sl1 and Sl2) and McCoy a and b (McCa and McCb), whose functional effects are unknown. We tested the hypothesis that the Sl and McC polymorphisms might influence CR1 clustering on erythrocyte membranes. Blood samples from 125 healthy Kenyan children were analysed by immunofluorescence and confocal microscopy to determine CR1 cluster number and volume. In agreement with previous reports, CR1 cluster number and volume were positively associated with CR1 copy number (mean number of CR1 molecules per erythrocyte). Individuals with the McC b /McC b genotype had more clusters per cell than McC a/McC a individuals. However, this association was lost when the strong effect of CR1 copy number was included in the model. No association was observed between Sl genotype, sickle cell genotype, α+thalassaemia genotype, gender or age and CR1 cluster number or volume. Therefore, after correction for CR1 copy number, the Sl and McCoy polymorphisms did not influence erythrocyte CR1 clustering, and the effects of the Knops polymorphisms on CR1 function remains unknown.

Two complement receptor one alleles have opposing associations with cerebral malaria and interact with α+thalassaemia

“…Previously, we have shown that neither cofactor activity for the breakdown of C3b and C4b nor binding to C1q are influenced by the Sl2 and McC b mutations ( Tetteh-Quarcoo et al, 2012 ). In addition, we can find no association between Knops genotype and CR1 clustering on erythrocytes ( Paccaud et al, 1988 ; Swann et al, 2017 ). However, other potential effects such as altered immune complex binding and processing or activation of the complement lectin pathway via mannose-binding lectin ( Ghiran et al, 2000 ) have not yet been investigated.…”