Effect of Intravenous immunoglobulin on Th1 and Th2 lymphocytes and improvement of pregnancy outcome in recurrent pregnancy loss

Majid Ahmadia,b,c,1 , Samaneh Abdolmohammadi-vahida,b,c,1 , Mahnaz Ghaebia,b,c , Leili Aghebati-Malekia,b,c , Amir Afkhamb,c , Shahla Danaiid , Sedigheh Abdollahi-Fardd , Lida Heidarid , Farhad Jadidi-Niaraghb,c , Vahid Younesie , Mohammad Nourif , Mehdi Yousefib,c, *

a Stem Cell and Regenerative Medicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran

bDrug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

c Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

dGynecology Department, Eastern Azerbaijan ACECR ART Center, Eastern Azerbaijan Branch of ACECR, Tabriz, Iran

ePishtaz Teb Zaman Diagnostics, Tehran, Iran

f Department of Biochemistry and Clinical Laboratories, Tabriz University of Medical Sciences, Tabriz, Iran


Background: Women with elevated natural killer (NK) cell frequency and function during pregnancy, suffer from recurrent pregnancy loss (RPL). In the present study, the possible effect of intravenous immunoglobulin (IVIG) administration on Th1 and Th2 cell frequency, cytokine secretion, and expression of transcription factors is compared between RPL patients and control group. Materials and methods: Totally, 44 women with a history of RPL (32 women as treated group and 12 as control group) were enrolled in the study. The frequency of Th1 and Th2 lymphocytes, the expression of transcription factors related to these cells and the serum levels of associated cytokines were assessed by flowcytometry, real-time PCR and ELISA, respectively. All, assessments were performed both before and after treatment with IVIG. Results: A significant reduction in Th1 lymphocyte frequency, transcription factor expression and cytokine levels were observed in IVIG-treated group, while all the above parameters indicated a significant increase for Th2 lymphocytes. Th1/Th2 ratio decreased significantly (p value < 0.0001) at the end of treatment and 28 out of 32 (87.5%) women in IVIG-treated group had live birth in comparison with 5 out of 12 (41.6%) in untreated group. Conclusion: IVIG administration proves to be an efficienttherapeutic strategy which is able to enhance the success rate of pregnancy through a shift in Th2 responses. Furthermore, IVIG presents efficacy for the treatment of reproduction failures especially in subjects with immune cell abnormalities and increased NK cell level and function


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