Molecular analysis of the York antigen of the Knops blood group system

Veldhuisen, Barbera; Ligthart, Peter; Vidarsson, Gestur; Roels, Ingrid; Folman, Claudia C.; Schoot, C. Ellen van der; Haas, Masja de

doi:10.1111/j.1537-2995.2010.02999.x

Cited by 12 publications

(5 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several antigens have been described in the Knops blood group system on CR1; Knops antigens a and b (Kn a /Kn b ), rs41274768 [19], McCoy a and b (McC a /McC b ), rs17047660 [20], Swain-Langley 1 and 2 (Sl1/Sl2), rs17047661 [20,21], KCAM + and - (KCAM + /KCAM - ), rs6691117 [22], York + and - (Yka + /Yka - ), rs3737002 [23] and Sl3,rs4844609 [21]. …”

Section: Introductionmentioning

confidence: 99%

Human genetic polymorphisms in the Knops blood group are not associated with a protective advantage against Plasmodium falciparum malaria in Southern Ghana

Hansson

Kurtzhals

Goka

et al. 2013

Malar J

View full text Add to dashboard Cite

BackgroundThe complex interactions between the human host and the Plasmodium falciparum parasite and the factors influencing severity of disease are still not fully understood. Human single nucleotide polymorphisms SNPs associated with Knops blood group system; carried by complement receptor 1 may be associated with the pathology of P. falciparum malaria, and susceptibility to disease.MethodsThe objective of this study was to determine the genotype and haplotype frequencies of the SNPs defining the Knops blood group antigens; Kna/b, McCoya/b, Swain-Langley1/2 and KCAM+/- in Ghanaian patients with malaria and determine possible associations between these polymorphisms and the severity of the disease. Study participants were patients (n = 267) admitted to the emergency room at the Department of Child Health, Korle-Bu Teaching Hospital, Accra, Ghana during the malaria season from June to August in 1995, 1996 and 1997, classified as uncomplicated malaria (n = 89), severe anaemia (n = 57) and cerebral malaria (n = 121) and controls who did not have a detectable Plasmodium infection or were symptomless carriers of the parasite (n = 275). The frequencies were determined using a post-PCR ligation detection reaction-fluorescent microsphere assay, developed to detect the SNPs defining the antigens. Chi-square/Fisher’s exact test and logistic regression models were used to analyse the data.ResultsAs expected, high frequencies of the alleles Kna, McCb, Sl2 and KCAM- were found in the Ghanaian population. Apart from small significant differences between the groups at the Sl locus, no significant allelic or genotypic differences were found between the controls and the disease groups or between the disease groups. The polymorphisms define eight different haplotypes H1(2.4%), H2(9.4%), H3(59.8%), H4(0%), H5(25.2%), H6(0.33%), H7(2.8%) and H8(0%). Investigating these haplotypes, no significant differences between any of the groups were found.ConclusionThe results confirm earlier findings of high frequencies of certain CR1 alleles in Africa; and shed more light on earlier conflicting findings; the alleles McCb, Sl2, Knb and KCAM- or combined haplotypes do not seem to confer any protective advantage against malaria infection or resulting disease severity. Based on these findings, in a very well-characterized population, malaria does not seem to be the selective force on these alleles.

show abstract

Section: Introductionmentioning

confidence: 99%

Human genetic polymorphisms in the Knops blood group are not associated with a protective advantage against Plasmodium falciparum malaria in Southern Ghana

Hansson

Kurtzhals

Goka

et al. 2013

Malar J

View full text Add to dashboard Cite

show abstract

“…Polymorphisms that alter CR1 gene expression or protein activity are also common worldwide (57–60) and have been associated with different infectious, autoimmune, and neurological/neurodegenerative diseases (61–67). Those in exon 29 encode antigens of the Knops blood group system, the 22nd system recognized by the International Society of Blood Transfusion (68): e.g., rs3737002 (p.Thr1408Met) defines the York blood antigen and rs17047660 (p.Lys1590Glu), the McCoy blood antigen (69, 70). These polymorphisms may modulate the success of Plasmodium falciparum and Leishmania major , as well as mycobacteria that invade erythrocytes and macrophages, respectively (71–75).…”

Section: Discussionmentioning

confidence: 99%

Complement Receptor 1 (CR1, CD35) Polymorphisms and Soluble CR1: A Proposed Anti-inflammatory Role to Quench the Fire of “Fogo Selvagem” Pemphigus Foliaceus

et al. 2019

View full text Add to dashboard Cite

Pemphigus foliaceus is an autoimmune disease that is sporadic around the world but endemic in Brazil, where it is known as fogo selvagem (FS). Characterized by autoantibodies against the desmosomal cadherin desmoglein 1, FS causes painful erosions, and crusts that may be widespread. The recognition of antigens, including exposed sugar moieties, activates the complement system. Complement receptor 1 (CR1, CD35), which is responsible for the Knops blood group on erythrocytes (York and McCoy antigens), is also expressed by antigen-presenting cells. This regulates the complement system by removing opsonized antigens, blocking the final steps of the complement cascade. Membrane-bound CR1 also fosters antigen presentation to B cells, whereas soluble CR1 has anti-inflammatory properties. CR1 gene polymorphisms have been associated with susceptibility to complex diseases. In order to investigate the association of CR1 polymorphisms with FS susceptibility, we developed a multiplex sequence-specific assay to haplotype eleven polymorphisms in up to 367 FS patients and 242 controls from an endemic area and 289 from a non-endemic area. We also measured soluble CR1 (sCR1) in the serum of 53 FS patients and 27 controls and mRNA levels in the peripheral blood mononuclear cells of 63 genotyped controls. The haplotypes CR1*3B2B (with the York antigen–encoded by p.1408Met) and CR1*3A2A (with p.1208Arg) were associated with protection against FS (OR = 0.57, P = 0.027, and OR = 0.46, P = 0.014, respectively). In contrast, the CR1*1 haplotype (with the McCoy antigen – encoded by p.1590Glu) was associated with FS susceptibility (OR = 4.97, P < 0.001). Heterozygote rs12034383*A/G individuals presented higher mRNA expression than homozygotes with the G allele (P = 0.04). The lowest sCR1 levels occurred in patients with active disease before treatment (P = 0.036). Patients in remission had higher levels of sCR1 than did healthy controls (P = 0.013). Among those under treatment, patients with localized lesions also presented higher sCR1 levels than those with generalized lesions (P = 0.0073). In conclusion, the Knops blood group seems to modulate susceptibility to the disease. Furthermore, corticosteroid treatment might increase sCR1 serum levels, and higher levels may play an anti-inflammatory role in patients with FS, limiting the distribution of lesions. Based on these results, we suggest CR1 as a potential new therapeutic target for the treatment of FS.

show abstract

“…Another CR1 polymorphism of interest relates to the Knops blood group system. This system consists of nine antigens (KN1-KN9) comprising the three antigenic pairs V1561M, K1590E and R1601G and one conformational epitope (R1601 with S1610) in CCP25, and the single antigens T1408 located in the linker between CCPs 22-23 and I1615 in CCP25 (Table 2) (Covas et al, 2007;Moulds et al, 1991Moulds et al, , 2002Moulds et al, , 2005Veldhuisen et al, 2011).…”

Section: Complement Receptor 1 and Malariamentioning

confidence: 99%