Intravenous immunoglobulin (IVIG) treatment modulates peripheral blood Th17 and regulatory T cells in recurrent miscarriage patients: Non randomized, open-label clinical trial

Majid Ahmadia,b,c,d, Sanaz Abbaspour aghdamd, Mohammad Nouria,e, Zohreh Babalood, Laya Farzadie, Aliye Ghasemzadehe, Kobra Hamdie, Ali Akbar Movassaghpourf,Farhad Jadidi-Niaraghb,d, Amir Afkhamd, Morteza Motallebnezhada,b, Shadi Eghbal-Fardd ,Sanam Dolatib,d, Vahid Younesig, Mehdi Yousefib,d,

a Stem Cell and Regenerative Medicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
b Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
c Student’s Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran d Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
e Reproductive Biology Department, Tabriz University of Medical Sciences, Tabriz, Iran

f Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
g Pishtaz Teb Diagnostics, Tehran, Iran

ABSTRACT

Background: Th17 cells and Treg cells have been proposed as new risk factors for recurrent miscarriage (RM). In this study, we investigated the effect of Intravenous immunoglobulin G (IVIG) on the levels and function of Th17 and Treg cells and pregnancy outcome in women with RM. Materials and methods: 94 pregnant women with RM were enrolled in this study. Blood was drawn at the time of positive pregnancy. On the same day, IVIG 400 mg/kg was administered intravenously for 44 patients. 50 other RM patients were included as no IVIG interfering control group. Following the first administration, IVIG was given every 4 weeks through 32 weeks of gestation. Peripheral blood was drawn after the last administration (32 weeks after pregnancy). Results: IVIG down-regulated Th17 cells population and function and up-regulated Treg cells population and function were significant in the treated group. Pregnancy outcome in IVIG treated subjects was successful in 38 out of 44 RM women (86.3%). However, pregnancy outcome was successful in 21 out of 50 untreated RM women (42%). Conclusion: Administration of IVIG in RM women with cellular immune cells abnormalities during pregnancy influences Th17/Treg ratio in peripheral blood and enhances Treg and decreases Th17 responses.

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