Upregulated serum granulysin levels in women with antiphospholipid antibody‐associated recurrent miscarriage are downregulated by heparin treatment

PURPOSE: Granulysin is a cytotoxic protein that simultaneously activates innate and cellular immunity. The authors aimed to evaluate whether granulysin is associated with the antiphospholipid antibody syndrome and whether heparin changes the granulysin levels. METHODS: A cohort study was performed with women with antiphospholipid antibody‐positive recurrent pregnancy loss (RPL). The authors examined granulysin levels under RPL and evaluated the changes in serum granulysin levels before and 1 week after the commencement of heparin treatment. RESULTS: Serum granulysin levels before heparin treatment were significantly higher in women who tested positive for one or more types of antiphospholipid antibodies (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, serum granulysin levels were significantly reduced (p = 0.0017 by the 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). CONCLUSION: The results suggest that heparin may reduce the incidence of miscarriage by suppressing serum granulysin levels.