Paternal HLA-C is a risk factor in unexplained recurrent miscarriage

Tess Meuleman; Geert W Haasnoot; Jan M M van Lith; Willem Verduijn; Kitty W M Bloemenkamp; Frans H J Claas

doi:10.1111/aji.12797

Paternal HLA-C is a risk factor in unexplained recurrent miscarriage

Tess Meuleman, Geert W Haasnoot, Jan M M van Lith, Willem Verduijn, Kitty W M Bloemenkamp, Frans H J Claas

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

PROBLEM: HLA-C is the only classical HLA-I antigen expressed on trophoblast. We hypothesized that the alloimmune response to paternal HLA-C plays a role in unexplained recurrent miscarriage.

METHOD OF STUDY: In a case-control design, we included 100 women with at least three unexplained consecutive miscarriages along with their partners and children. For the first control group, we included 90 women with an uneventful singleton pregnancy without pregnancy complications in their history along with their children. The second control group consisted of 425 families. HLA-C*07 and HLA-C*17 frequencies, which are the most immunogenic HLA-C antigens, along with HLA-C mismatches, and the presence of specific HLA antibodies in the mother were determined.

RESULTS: HLA-C and HLA-C*07 mismatches were significantly increased in couples with recurrent miscarriage compared to control subjects (P = .016, P = .008, respectively). The incidence of child-specific HLA-C*07/HLA-C*17 antibodies was increased in women with recurrent miscarriage (P = .007).

CONCLUSION: The results show that HLA-C incompatibility between couples is significantly associated with unexplained recurrent miscarriage.

Original language	English
Article number	e12797
Pages (from-to)	1-9
Journal	American Journal of Reproductive Immunology
Volume	79
Issue number	2
DOIs	https://doi.org/10.1111/aji.12797
Publication status	Published - 1 Feb 2018

Keywords

HLA-C
pregnancy
recurrent miscarriage

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10.1111/aji.12797

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title = "Paternal HLA-C is a risk factor in unexplained recurrent miscarriage",

abstract = "PROBLEM: HLA-C is the only classical HLA-I antigen expressed on trophoblast. We hypothesized that the alloimmune response to paternal HLA-C plays a role in unexplained recurrent miscarriage.METHOD OF STUDY: In a case-control design, we included 100 women with at least three unexplained consecutive miscarriages along with their partners and children. For the first control group, we included 90 women with an uneventful singleton pregnancy without pregnancy complications in their history along with their children. The second control group consisted of 425 families. HLA-C*07 and HLA-C*17 frequencies, which are the most immunogenic HLA-C antigens, along with HLA-C mismatches, and the presence of specific HLA antibodies in the mother were determined.RESULTS: HLA-C and HLA-C*07 mismatches were significantly increased in couples with recurrent miscarriage compared to control subjects (P = .016, P = .008, respectively). The incidence of child-specific HLA-C*07/HLA-C*17 antibodies was increased in women with recurrent miscarriage (P = .007).CONCLUSION: The results show that HLA-C incompatibility between couples is significantly associated with unexplained recurrent miscarriage.",

keywords = "HLA-C, pregnancy, recurrent miscarriage",

author = "Tess Meuleman and Haasnoot, {Geert W} and {van Lith}, {Jan M M} and Willem Verduijn and Bloemenkamp, {Kitty W M} and Claas, {Frans H J}",

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AU - Meuleman, Tess

AU - Haasnoot, Geert W

AU - van Lith, Jan M M

AU - Verduijn, Willem

AU - Bloemenkamp, Kitty W M

AU - Claas, Frans H J

PY - 2018/2/1

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N2 - PROBLEM: HLA-C is the only classical HLA-I antigen expressed on trophoblast. We hypothesized that the alloimmune response to paternal HLA-C plays a role in unexplained recurrent miscarriage.METHOD OF STUDY: In a case-control design, we included 100 women with at least three unexplained consecutive miscarriages along with their partners and children. For the first control group, we included 90 women with an uneventful singleton pregnancy without pregnancy complications in their history along with their children. The second control group consisted of 425 families. HLA-C*07 and HLA-C*17 frequencies, which are the most immunogenic HLA-C antigens, along with HLA-C mismatches, and the presence of specific HLA antibodies in the mother were determined.RESULTS: HLA-C and HLA-C*07 mismatches were significantly increased in couples with recurrent miscarriage compared to control subjects (P = .016, P = .008, respectively). The incidence of child-specific HLA-C*07/HLA-C*17 antibodies was increased in women with recurrent miscarriage (P = .007).CONCLUSION: The results show that HLA-C incompatibility between couples is significantly associated with unexplained recurrent miscarriage.

AB - PROBLEM: HLA-C is the only classical HLA-I antigen expressed on trophoblast. We hypothesized that the alloimmune response to paternal HLA-C plays a role in unexplained recurrent miscarriage.METHOD OF STUDY: In a case-control design, we included 100 women with at least three unexplained consecutive miscarriages along with their partners and children. For the first control group, we included 90 women with an uneventful singleton pregnancy without pregnancy complications in their history along with their children. The second control group consisted of 425 families. HLA-C*07 and HLA-C*17 frequencies, which are the most immunogenic HLA-C antigens, along with HLA-C mismatches, and the presence of specific HLA antibodies in the mother were determined.RESULTS: HLA-C and HLA-C*07 mismatches were significantly increased in couples with recurrent miscarriage compared to control subjects (P = .016, P = .008, respectively). The incidence of child-specific HLA-C*07/HLA-C*17 antibodies was increased in women with recurrent miscarriage (P = .007).CONCLUSION: The results show that HLA-C incompatibility between couples is significantly associated with unexplained recurrent miscarriage.

KW - HLA-C

KW - pregnancy

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Paternal HLA-C is a risk factor in unexplained recurrent miscarriage

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