Novel autoantibody a major risk factor for recurrent pregnancy loss

A team of Japanese researchers identified a novel antibody (neo-self antibody) as a major risk factor for recurrent pregnancy loss (RPL), according to their findings published in the American College of Rheumatology’s journal ‘Arthritis and Rheumatology’.¹

Faculty from Kobe University’s Graduate School of Medicine and Osaka University’s Research Institute for Microbial Diseases (RIMD) led this study, and in 2015, their joint research efforts led to the discovery of a completely new autoantibody that causes antiphospholipid syndrome.² This syndrome can cause thrombosis, miscarriages, and hypertensive disorders of pregnancy.

While RPL involving repeated miscarriages is a clinical manifestation of antiphospholipid syndrome, its cause is unknown in more than half of cases. The connection between this new neo-self antibody, discovered by the research team in 2015, and RPL in cases with unexplained causes, had not been investigated prior to this study.¹

Nearly 1.5 million women in Japan suffer from RPL, but the cause in more than half of cases is undetermined, which may be a contributing factor for the country’s low birthrates.¹ When combined with Japan’s aging population, the need for further understanding, treatment and prevention of RPL is emphasized as a major priority.

Researchers began the analyses with data from 227 patients affected by RPL in five university hospitals nationwide (Kobe University, University of Toyama, Okayama University, The University of Tokyo, and Hyogo Medical University).

They tested 208 women without RPL who previously gave birth to healthy babies to establish normal levels before testing blood samples from the affected patients. The results showed that 52 (23%) out of 227 patients with RPL tested positive for the neo-self antibody.

Causes of RPL were also investigated in each case, which included testing for thyroid disorders, uterine issues, chromosomal abnormalities and blood test analyses. In comparison to all other factors, the neo-self antibody presented with the highest frequency.

Even after testing for common RPL causes, it could not be determined in 53% (121) of patients; however, 24% of them tested positive for the neo-self antibody. Many patients who tested negative using conventional antiphospholipid antibody criteria also tested positive for the neo-self antibody.

The results of this study allowed researchers to identify the onset mechanism of RPL, especially in some cases that would have otherwise remained unexplained.

The importance of these findings should not be understated; they may also lead to the illumination of onset mechanisms for other adverse obstetric outcomes, such as unexplained hypertensive disorders of pregnancy and fetal growth restriction.

References

1. Tanimura K, Shigeru S, Nakatsuka M, et. al. The β2‐glycoprotein I/HLA‐DR complex is the major autoantibody target in obstetric antiphospholipid syndrome. Arthritis Rheumatol (2020). doi:10.1002/art.41410
2. Arase H, Tanimura K, et. al. Major Targets for Autoantibodies Causing Recurrent Miscarriage and Thrombosis Elucidated. Blood. https://resou.osaka-u.ac.jp/en/research/2015/20150303_1