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Combinations of maternal KIR and fetal HLA-C genes influence the risk of preeclampsia and reproductive success

  1. Author:
    Hiby, S. E.
    Walker, J. J.
    O'Shaughnessy, K. M.
    Redman, C. W. G.
    Carrington, M.
    Trowsdale, J.
    Moffett, A.

  2. Author Address

    Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England. St James Univ Hosp, Dept Obstet & Gynecol, Leeds LS9 7TF, W Yorkshire, England. Univ Cambridge, Addenbrookes Hosp, Sch Clin, Dept Med, Cambridge CB2 2QQ, England. Univ Oxford, John Radcliffe Hosp, Nuffield Dept Obstet & Gynecol, Oxford, England. SAIC Frederick Inc, Basic Res Program, NCI, Frederick, MD 21702 USA Moffett, A, Univ Cambridge, Dept Pathol, Tennis Court Rd, Cambridge CB2 1QP, England
    1. Year: 2004
    2. Date: OCT 18
  2. Journal: Journal of Experimental Medicine
    1. 200
    2. 8
    3. Pages: 957-965
  4. Type of Article: Article
  1. Abstract:

    Preeclampsia is a serious complication of pregnancy in which the fetus receives an inadequate supply of blood due to failure of trophoblast invasion. There is evidence that the condition has an immunological basis. The only known polymorphic histocompatibility antigens on the fetal trophoblast are HLA-C molecules. We tested the idea that recognition of these molecules by killer immunoglobulin receptors (KIRs) on maternal decidual NK cells is a key factor in the development of preeclampsia. Striking differences were observed when these polymorphic ligand: receptor pairs were considered in combination. Mothers lacking most or all activating KIR (AA genotype) when the fetus possessed HLA-C belonging to the HLA-C2 group were at a greatly increased risk of preeclampsia. This was true even if the mother herself also had HLA-C2, indicating that neither nonself nor missing-self discrimination was operative. Thus, this interaction between maternal KIR and trophoblast appears not to have an immune function, but instead plays a physiological role related to placental development. Different human populations have a reciprocal relationship between AA frequency and HLA-C2 frequency, suggesting selection against this combination. In light of our findings, reproductive success may have been a factor in the evolution and maintenance of human HLA-C and KIR polymorphisms

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External Sources

  1. View record in Web of Science®
  2. WOS: 000224677900002

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