A successful pregnancy after decrease of elevated uterine CD57+ natural killer cells by adalimumab therapy in a patient with rheumatoid arthritis in remission and a recent unexplained miscarriage 

蔡鋒博*¹ 陳昭雯¹ 陳信華²

1彰化市 博元婦產科診所 試管嬰兒中心 2台中榮民總醫院過敏免疫風濕科

Feng-Po Tsai¹, Chao-Wen Chen¹, Hsin-Hua Chen²

1 Poyuan Women Clinic, IVF center; Section of Allergy, 2 Immunology and Rheumatology, Taichung Veterans General Hospital

Introduction: Adalimumab (Humira, Abbot) is a recombinant monoclonal antibody that binds to human tumor necrosis factor (TNF-alpha) thereby interfering with endogenous TNF-alpha activity. Increased TNF-alpha levels have been associated with preeclampsia, miscarriage and infertility in both animal models and humans.  TNF-alpha can activate uterine NK cells to attack trophoblast directly or induce trophoblast apoptosis through TNF-alpha produced by activated uterine NK cells. Increased trophoblast debris production can cause macrophages to secrete excessive T helper 1 cytokines which lead to excessive inflammation and thereafter miscarriage.  Although there is interest in the use of TNF inhibitors to prevent pregnancy loss in patients at risk, only 2 relevant cases have been reported. Herein we reported a successful pregnancy after decreasing the elevated uterine CD57+ NK cells by adalimumab therapy in a patient with a previously unexplained miscarriage and rheumatoid arthritis in remission status. 

Case report: A 32 year-old Taiwanese woman presented in 2006 with rheumatoid arthritis in remission status and a recent unexplained miscarriage at 9 ^th gestational week. She received uterine curettage in July, 2006 because of fetal demise and the decidual tissue was sent for immunohistochemistry study, which disclosed marked   increase of CD57⁺ NK cells (28.2/high power field (HPF). Increased percentage of CD3^-CD16⁺ CD56⁺ NK cells (29%) in peripheral blood mononuclear cells was also noted. She received four doses of adalimumab injection and then another endometrial biopsy was performed on cycle day 26 in Jan. 2007. The number of CD57+ NK cells dropped significantly (1.3/HPF). The percentage of CD3^-CD16⁺ CD56⁺ NK cells in PBMC also decreased to 11.9%. She got pregnant spontaneously in Feb, 2007. She is now at 24 ^thgestational week in stable condition.