Upregulated Serum Granulysin Levels in Women With Antiphospholipid Syndrome-Associated Recurrent Miscarriages Are Downregulated by Heparin Treatment

Background Antiphospholipid antibody syndrome is the major cause of recurrent pregnancy loss (RPL) and associated with inflammation. Granulysin is a cytotoxic protein secreted by cytotoxic T cells, natural killer cells, and natural killer T cells that is present in abundance in the decidua. It activates innate and cellular immunity simultaneously, and also induces miscarriage. As a treatment, heparin is widely used for the patients with RPL, and exhibits the antithrombotic and anti-inflammatory activities, and angiogenesis. Methods We hypothesized that granulysin is an important factor in inducing miscarriage. Here, we evaluated the changes of serum granulysin level before and 1 week after the commencement of heparin treatment for the patients with RPL. Results The serum granulysin levels before heparin treatment were significantly higher in women who tested positive for one or more types of antiphospholipid antibody (2.75 ± 1.03 vs. 2.44 ± 0.69; P = 0.0341 by Welch’s t-test), particularly anti-phosphatidylethanolamine antibodies (IgG: 2.98 ± 1.09 vs. 2.51 ± 0.86; P = 0.0013, IgM: 2.85 ± 1.09 vs. 2.47 ± 0.77; P = 0.0024 by Welch’s t-test). After heparin treatment for 1 week, the serum granulysin levels were reduced significantly (P = 0.0017 by paired t-test). The miscarriage rate was significantly higher in women whose serum granulysin levels were not reduced by heparin treatment (P = 0.0086 by Fisher’s exact probability test). Conclusions These results suggest that heparin may reduce the incidence of miscarriages by suppressing the serum granulysin levels.