Phenotypic characterization of NKT-like cells and evaluation of specifically related cytokines for the prediction of unexplained recurrent miscarriage

Wafaa S Khalaf; Mohammad R A Mahmoud; Walid F Elkhatib; Hany R Hashem; Wafaa E Soliman

doi:10.1016/j.heliyon.2021.e08409

Phenotypic characterization of NKT-like cells and evaluation of specifically related cytokines for the prediction of unexplained recurrent miscarriage

Heliyon. 2021 Nov 16;7(11):e08409. doi: 10.1016/j.heliyon.2021.e08409. eCollection 2021 Nov.

Authors

Wafaa S Khalaf¹, Mohammad R A Mahmoud², Walid F Elkhatib^{3

4}, Hany R Hashem^{5

6}, Wafaa E Soliman^{7

8}

Affiliations

¹ Department of Microbiology and Immunology, Faculty of Pharmacy (Girls), Al-Azhar University, Nasr city, Cairo 11751, Egypt.
² Department of Obstetrics and Gynaecology, Faculty of Medicine, Al-Azhar University, Nasr city, Cairo 11751, Egypt.
³ Department of Microbiology and Immunology, Faculty of Pharmacy, Ain Shams University, African Union Organization St., Abbassia, Cairo 11566, Egypt.
⁴ Department of Microbiology and Immunology, Faculty of Pharmacy, Galala University, New Galala city, Suez, Egypt.
⁵ Department of Microbiology and Immunology, Faculty of Pharmacy, Fayoum University, Al- Fayoum 63514, Egypt.
⁶ Department of Microbiology and Immunology, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr city, Cairo 11829, Egypt.
⁷ Microbiology and Immunology Department, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, Mansoura, Egypt.
⁸ Biomedical Sciences Department, College of Clinical Pharmacy, King Faisal University, Al-Hofuf 36362, Al-Ahsa, Saudi Arabia.

Abstract

Problem: Immune system dysregulation is a major cause of unexplained recurrent miscarriage (URM). Women with URM need screening for their pregnancy microenvironment and immune regulators, to prevent spontaneous abortion.

Method of study: In this study we evaluated NKT-like cell subsets in peripheral venous blood of women with URM using flow cytometry. The expression levels of specifically related Th1 cytokines (IFN-γ and IL-2), Th2 cytokine (IL-4), and Th17 cytokines (IL-17), were measured using enzyme-linked immunosorbent assay.

Results: The percentage of CD16+CD56+NKT-like (Double Positive NKT-like; DPNKT-like) cell subset, and the levels of IL-2 and IFN-γ were significantly elevated in blood of non-pregnant and pregnant patients with URM compared with the healthy control groups, and these parameters were significantly increased after pregnancy in the same patients with URM. Based on the prevalence of the candidate immunological factors in patients with URM, the prognostic significance of the NKT-like cell subsets, IFN-γ and IL-2 profiles were evaluated as potential predictors of URM. A cut-off point of 2.55% for DPNKT-like cell subset in the blood and cut-off values of 39.5 and 20.5 pg/ml for the levels of IFN-γ and IL-2, respectively could be used for the prediction of the risk of spontaneous abortion. To the best of our knowledge, this is the first study that described the prognostic significance of the aforementioned immunological parameters before and after pregnancy, and highlighted the correlation of NKT-like cells and the candidate Th1 cytokines with pregnancy loss in women with URM.

Conclusions: DPNKT-like cells, IFN-γ and IL-2 patient profiles could be used as markers to predict the risk of miscarriage in patients with URM.

Keywords: Cytokines; NKT-like cells; Prediction; Unexplained recurrent miscarriage.