Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2024 Sep 26:15:1445852.
doi: 10.3389/fimmu.2024.1445852. eCollection 2024.

Low-dose aspirin and heparin treatment improves pregnancy outcome in recurrent pregnancy loss women with anti-β2-glycoprotein I/HLA-DR autoantibodies: a prospective, multicenter, observational study

Kenji Tanimura  1 , Shigeru Saito  2 , Sayaka Tsuda  2 , Yosuke Ono  3 , Masashi Deguchi  1 , Takeshi Nagamatsu  4   5 , Tomoyuki Fujii  4   5   6 , Mikiya Nakatsuka  7 , Gen Kobashi  8 , Hisashi Arase  9 , Hideto Yamada  1   10
Affiliations
Observational Study

Low-dose aspirin and heparin treatment improves pregnancy outcome in recurrent pregnancy loss women with anti-β2-glycoprotein I/HLA-DR autoantibodies: a prospective, multicenter, observational study

Kenji Tanimura et al. Front Immunol. .

Abstract

Introduction: Anti-β2-glycoprotein I (β2GPI)/human leukocyte antigen (HLA)-DR antibodies may be a risk factor for recurrent pregnancy loss (RPL). The therapeutic modality for women with RPL and anti-β2GPI/HLA-DR antibody positivity has not been evaluated. This prospective, multicenter, observational study aimed to assess whether low-dose aspirin (LDA) and/or heparin therapies improve pregnancy outcomes in women with RPL who tested positive for anti-β2GPI/HLA-DR antibodies.

Methods: Between August 2019 and December 2021, 462 women with RPL underwent anti-β2GPI/HLA-DR antibody measurements and risk assessments for RPL. Each attending physician decided the treatment modality for women with RPL who tested positive for anti-β2GPI/HLA-DR antibodies, and their pregnancy outcomes were followed up until December 2023. Finally, 47 pregnancies in 47 women with RPL and anti-β2GPI/HLA-DR antibody positivity were included in the analysis and were divided into two groups regarding whether they were treated with LDA and/or unfractionated heparin (UFH) (LDA/UFH group, n = 39) or with neither of them (non-LDA/non-UFH group, n = 8). The rates of live birth and pregnancy complications (i.e., preeclampsia and preterm delivery before 34 gestational weeks due to placental insufficiency) were compared between the two groups.

Results: The live birth rate in the LDA/UFH group was higher than that in the non-LDA/non-UFH group (87.2% vs 50.0%, p = 0.03). The pregnancy complication rate in the LDA/UFH group was significantly lower than that in the non-LDA/non-UFH group (5.9% vs 50.0%, p = 0.048). Among 21 women who tested positive for anti-β2GPI/HLA-DR antibodies and had no other risk factors for RPL, the live birth rate in the LDA/UFH group (n = 14) was much higher than that in the non-LDA/non-UFH group (n = 7) (92.9% vs 42.9%, p = 0.03).

Discussion: This study, for the first time, demonstrated that LDA and/or UFH therapies are effective in improving pregnancy outcomes in women with RPL and aβ2GPI/HLA-DR antibody positivity.

Keywords: anti-β2-glycoprotein I/HLA-DR antibody; low-dose aspirin; pregnancy complications; recurrent pregnancy loss; treatment; unfractionated heparin.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow diagram of the participants and their pregnancies included in the final analysis. RPL, recurrent pregnancy loss; β2GPI, β2-glycoprotein I; HLA, human leukocyte antigen; IUFD, intrauterine fetal death.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Jiang Y, Arase N, Kohyama M, Hirayasu K, Suenaga T, Jin H, et al. . Transport of misfolded endoplasmic reticulum proteins to the cell surface by MHC class II molecules. Int Immunol. (2013) 25:235–46. doi: 10.1093/intimm/dxs155 - DOI - PMC - PubMed
    1. Jin H, Arase N, Hirayasu K, Kohyama M, Suenaga T, Saito F, et al. . Autoantibodies to IgG/HLA class II complexes are associated with rheumatoid arthritis susceptibility. Proc Natl Acad Sci U.S.A. (2014) 111:3787–92. doi: 10.1073/pnas.1401105111 - DOI - PMC - PubMed
    1. Jin H, Kishida K, Arase N, Matsuoka S, Nakai W, Kohyama M, et al. . Abrogation of self-tolerance by misfolded self-antigens complexed with MHC class II molecules. Sci Adv. (2022) 8:eabj9867. doi: 10.1126/sciadv.abj9867 - DOI - PMC - PubMed
    1. Tsuji H, Ohmura K, Jin H, Naito R, Arase N, Kohyama M, et al. . Anti-double-stranded DNA antibodies recognize DNA presented on HLA class II molecules of systemic lupus erythematosus risk alleles. Arthritis Rheumatol. (2022) 74:105–11. doi: 10.1002/art.41897 - DOI - PubMed
    1. Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, et al. . International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. (2006) 4:295–306. doi: 10.1111/j.1538-7836.2006.01753.x - DOI - PubMed

Publication types

MeSH terms