Donor HLA-C Genotype Has a Profound Impact on the Clinical Outcome Following Liver Transplantation

Hanvesakul, Raj; Spencer, Neil; Cook, Mark; Gunson, Bridget K.; Hathaway, Mark; Brown, RM; Nightingale, Peter; Cockwell, Paul; Hübscher, Stefan G.; Adams, David H.; Moss, Paul; Briggs, David

doi:10.1111/j.1600-6143.2008.02341.x

Cited by 67 publications

(60 citation statements)

References 43 publications

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“…on May 12, 2018. by guest www.bloodjournal.org From impact on the outcome of liver transplants. 65 HLA-C is the major inhibitory ligand for killer cell immunoglobulin-like receptors (KIRs). KIR genes are highly polymorphic and are expressed on natural killer cells and a subset of T lymphocytes.…”

Section: Org Frommentioning

confidence: 99%

The relationship between blood groups and disease

Anstee

2010

Blood

378

349

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The relative contribution of founder effects and natural selection to the observed distribution of human blood groups has been debated since blood group frequencies were shown to differ between populations almost a century ago. Advances in our understanding of the migration patterns of early humans from Africa to populate the rest of the world obtained through the use of Y chromosome and mtDNA markers do much to inform this debate. There are clear examples of protection against infectious diseases from inheritance of polymorphisms in genes encoding and regulating the expression of ABH and Lewis antigens in bodily secretions particularly in respect of Helicobacter pylori, norovirus, and cholera infections. However, available evidence suggests surviving malaria is the most significant selective force affecting the expression of blood groups. IntroductionHirszfeld and Hirszfeld 1 showed the frequencies of blood groups A and B differ between populations. Their observations raised fundamental questions regarding the causes of these differences, which were eloquently summarized by Mourant et al 2(p1) :Were the differences the result of random genetic drift and founder effects, in small populations which later multiplied and stabilized the original, fortuitous, frequencies, or were they the result of natural selection, arising from differences in fitness between the various blood groups, fitnesses which themselves depended upon locally determined features of the external environment?Mourant et al concluded that "most workers now agree that both processes are operative, but their relative importance remains in question." 2 We now have detailed information concerning almost all the genes giving rise to blood group polymorphisms, the structure of the gene products and the antigens themselves, and in many cases functional information sufficient to delineate mechanisms of interaction with external agents. [3][4][5] In addition, studies on the tracking of Y chromosome and mtDNA haplotypes in human populations provide us with unprecedented information concerning the significance of genetic drift and founder effects in determining the genetic background of different world populations. 6 Given this new information, it seems an appropriate time to revisit these questions and ask whether we are any nearer understanding the relative importance of natural selection and founder effects in determining the distribution of human blood groups. Infectious diseases and selection for ABO blood group antigensThe molecular basis of the ABO blood group system was elucidated in 1990. 7 The gene encodes a glycosyltransferase, which transfers N-acetyl D-galactosamine (group A) or D-galactose (group B) to the nonreducing ends of glycans on glycoproteins and glycolipids. The group O phenotype results from inactivation of the A1 glycosyltransferase gene, and the nonreducing ends of the corresponding glycans in group O subjects express the blood group H antigen ( Figure 1A). The ABH antigens are not confined to red cells but are widely expressed i...

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Section: Org Frommentioning

confidence: 99%

The relationship between blood groups and disease

Anstee

2010

Blood

378

349

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“…12,27 Another study showed significantly decreased graft survival in the presence of 0 or 1 mismatch compared with 2 HLA-DR mismatches, with decreased risk for developing recurrent primary sclerosing cholangitis with 2 HLA-DR mismatches. 26 It has been hypothesized that human leukocyte antigen mismatching may act beneficially by decreasing the effects of immunologic mechanisms associated with disease recurrence in patients transplanted for autoimmune diseases. 40 The human leukocyte antigen mismatching at all loci positively affects patients transplanted for autoimmune hepatitis, 41 and a negative effect of DR mismatching has been noted on graft survival in patients with autoimmune hepatitis.…”

Section: Discussionmentioning

confidence: 99%

“…A previous study showed an effect of HLA-C on chronic rejection and graft loss. 26 The HLA-C alleles may be important as ligands for killer immunoglobulinlike receptors. These receptors are present on NK cells and some T lymphocytes and may affect cytotoxicity.…”

Section: Discussionmentioning

confidence: 99%

“…12,24,25 The effect of HLA-C on liver transplant is controversial. Although the HLA-C2 genotype of donors may positively affect chronic rejection and graft cirrhosis, 26 there is no effect of HLA-C2 genotype on long-term outcome. 27 Although patients who have liver transplant for primary sclerosing cholangitis may have good longterm survival, there is potential morbidity for biliary complications, especially in young patients who often have minor comorbidities.…”

Section: Introductionmentioning

confidence: 99%

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Survival Without Biliary Complications After Liver Transplant for Primary Sclerosing Cholangitis

Mogl

Albert²,

Pascher³

et al. 2013

Exp Clin Transplant

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Objectives: Patients who have a liver transplant for primary sclerosing cholangitis may develop recurrent disease and biliary complications, organ loss necessitating revision liver transplant, or death. We evaluated long-term outcomes in patients who had liver transplant for primary sclerosing cholangitis. Materials and Methods: In 71 patients who had a liver transplant for end-stage liver disease because of primary sclerosing cholangitis, a retrospective review was done to evaluate biliary complicationfree survival, transplanted organ survival, and death. Human leukocyte antigen typing and matching were reviewed. Results: There were 39 patients (55%) who had biliary complications, loss of the liver transplant, or death at a mean 12.1 years after transplant. The 5-and 10-year event-free survival reached 74.6% and 45% (53 patients after 5 years, and 32 patients after 10 years). Male sex of transplant recipients was a significant risk factor for biliary complications, revision liver transplant, or death. Most patients had inflammatory bowel disease, primarily ulcerative colitis. The human leukocyte antigen profile or number of mismatches had no effect on complication-free survival. Conclusions: Biliary complications, revision liver transplant, and death are a useful combined primary endpoint for recurrent primary sclerosing cholangitis after liver transplant.

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“…While recognition of HLA mismatch by T cells is well established as the main driver of graft rejection in other solid organ transplants, HLA cross-matching is not normally performed prior to LT. Any role for HLA matching in LT remains controversial. Early studies of HLA-C disparity between donor and recipient showed correlation between HLA-C matching, reduction in acute rejection rate, and increased graft survival (35,36). Increased expression of the KIR2D receptors on recipient NK cells, which is responsible for the recognition of HLA-C epitopes, also correlated with increased graft survival and fewer episodes of rejection (37).…”

Section: Nk Cells In Rejectionmentioning

confidence: 99%