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Hum. Reprod. Advance Access published online on March 11, 2009
Human Reproduction, doi:10.1093/humrep/dep047
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© The Author 2009. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Influence of activating and inhibitory killer immunoglobulin-like receptors on predisposition to recurrent miscarriages

R.M. Faridi1, V. Das2, G. Tripthi1, S. Talwar1, F. Parveen1 and S. Agrawal1,3

1 Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, Uttar Pradesh 226014, India 2 Department of Obstetrics and Gynaecology, Queen Mary Hospital, CSM Medical University, Lucknow, Uttar Pradesh, India

3 Correspondence address. Tel: +91-522-668004-8 ext. 2338, 2346, 2347, 2339; Fax: +91-522-6680973/6680017; E-mail: suraksha{at}sgpgi.ac.in

BACKGROUND: Understanding of the immune events and mechanisms occurring at the feto–maternal interface is likely to help in understanding the ability of the fetus to survive within the maternal body. Evidence supporting extensive roles of natural killer cells during pregnancy gives rise to a possibility that these NK cells can be mis-regulated and involved in fetal allograft rejection. Killer immunoglobulin-like receptors (KIR) play an important role in regulating the NK cell activity through their activating and inhibiting isoforms. Since there exists a considerable, genetically determined variation in the repertoire of KIR receptors between different individuals, a particular maternal KIR repertoire may predispose to recurrent miscarriages (RMs).

METHODS: Gene-specific PCR amplification (PCR-SSP) was used to determine the individual KIR genotypes in women experiencing RM and controls.

RESULTS: A higher prevalence of activating KIR genes was seen in patients than in controls. Among women experiencing RM, the BB genotypes were more prevalent (P < 0.0001, OR = 4.4, 95% CI = 2.89–6.69) compared with controls.

CONCLUSIONS: Our results indicate that the balance between inhibitory and activating receptor-mediated signals present in natural killer cells is inclined toward a more activating state that may contribute to pregnancy loss.

Key words: recurrent miscarriages/natural killer cells/trophoblast/activating and inhibitory killer immunoglobulin-like receptors

Submitted on July 18, 2008; resubmitted on January 31, 2009; accepted on February 4, 2009.


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