Pathogenesis of autoimmune diseases associated with 8.1 ancestral haplotype: a genetically determined defect of C4 influences immunological parameters of healthy carriers of the haplotype

Candore, Giuseppina; Modica, Maria Assunta; Lio, Domenico; Colonna‐Romano, Giuseppina; Listı́, Florinda; Grimaldi, Maria Paola; Russo, Mariangela; Triolo, G; Accardo-Palumbo, Antonina; Cuccia, M.; Caruso, Calogero

doi:10.1016/s0753-3322(03)00079-9

Cited by 43 publications

(50 citation statements)

References 17 publications

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“…The common European 8.1 ancestral haplotype (HLA-A1, B8, DR3) carries a single C4B and no C4A gene. 19,20 Consequently, it was highly prevalent among recipients and donors with low C4 gene dosage (39.4 and 26.8%, respectively), which resulted in their having better HLA-matched grafts (Table 2).…”

Section: C4 Genotyping Resultsmentioning

confidence: 99%

Genotypic Diversity of Complement Component C4 Does Not Predict Kidney Transplant Outcome

Wahrmann¹,

Döhler²,

Ruhenstroth³

et al. 2011

Journal of the American Society of Nephrology

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Gene copy number of complement component C4, which varies among individuals, may determine the intrinsic strength of the classical complement pathway. Presuming a major role of complement as an effector in transplant rejection, we hypothesized that C4 genetic diversity may partially explain the variation in allograft outcomes. This retrospective study included 1969 deceased-donor kidney transplants randomly selected from the Collaborative Transplant Study DNA bank. We determined recipient and donor gene copy number of total C4, C4 isotypes (C4A and C4B), and C4 gene length variants (C4L and C4S) by quantitative real-time PCR analysis. Groups defined according to recipient C4 gene copy number (low, intermediate, and high) had similar 10-year allograft survival. Genotypic groups showed comparable rates of graft dysfunction, treatment for rejection, immunological graft loss, hospitalization for infection, malignant disease, and death. Similarly, separate analyses of C4A, C4B, C4L, and C4S; combined evaluation of donor and recipient C4 genotype; or analysis of recipients with higher risk for rejection did not reveal considerable outcome effects. In conclusion, we did not demonstrate that C4 gene copy number associates with transplant outcome, and we found no evidence that the resulting variation in the strength of classical complement activation influences susceptibility to rejection.

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Section: C4 Genotyping Resultsmentioning

confidence: 99%

Genotypic Diversity of Complement Component C4 Does Not Predict Kidney Transplant Outcome

Wahrmann¹,

Döhler²,

Ruhenstroth³

et al. 2011

Journal of the American Society of Nephrology

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show abstract

“…The haplotype HLA-DRB1*03:01 with C4A deficiency and 1 C4B gene was positively associated with resolved disease when compared with controls (Table 3). Of all DRB1*03:01 alleles, 67 (resolved), 89 (persistent), and 66% (controls) were inherited with the "8.1 ancestral haplotype" [35].…”

Section: Hla Haplotype and Ld Analysismentioning

confidence: 99%

HLA-DRB1 allele frequencies and C4 copy number variation in Finnish sarcoidosis patients and associations with disease prognosis

et al. 2012

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“…Yet, among the Caucasians the number of autoimmune diseases have been shown to be associated with the HLA-DRB1*03 genotype. Importantly, healthy individuals with this allele have a number of immunological abnormalities including a changed cytokine production pattern and changed apoptosis mechanisms in T and B cells, or a defect of C4 in persons with the ancestral haplotype which includes HLA-DRB1*0301 [6,7]. All these abnormalities can increase the risk for developing autoimmunity.…”

Section: Introductionmentioning

confidence: 99%

Demonstration of high prevalence of SS-A antibodies in a general population: Association with HLA-DR and enterovirus antibodies

et al. 2006

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Pathogenesis of autoimmune diseases associated with 8.1 ancestral haplotype: a genetically determined defect of C4 influences immunological parameters of healthy carriers of the haplotype

Cited by 43 publications

References 17 publications

Genotypic Diversity of Complement Component C4 Does Not Predict Kidney Transplant Outcome

Genotypic Diversity of Complement Component C4 Does Not Predict Kidney Transplant Outcome

HLA-DRB1 allele frequencies and C4 copy number variation in Finnish sarcoidosis patients and associations with disease prognosis

Demonstration of high prevalence of SS-A antibodies in a general population: Association with HLA-DR and enterovirus antibodies

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