Heparin and aspirin combination therapy restores T-cell phenotype in pregnant patients with antiphospholipid syndrome-related recurrent pregnancy loss

Wang, Meiying; Zhang, Peng; Yu, Shengyan; Zhou, Gengmin; Lv, Jiyang; Nallapothula, Dhiraj; Guo, Chengshan; Wang, Qingwen; Singh, Ram Raj

doi:10.1016/j.clim.2019.108259

Cited by 11 publications

(11 citation statements)

References 43 publications

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“…In addition, the local immune micromilieu is better adjusted to immune tolerance, resulting in improved endometrial receptivity and increased local blood supply. These changes promote embryo implantation while reducing the formation of microthrombi in the placenta, all of which play an important role in the implantation and maintenance of the embryo ( 40 – 42 ).…”

Section: Discussionmentioning

confidence: 99%

Anticardiolipin and/or anti-β2-glycoprotein-I antibodies are associated with adverse IVF outcomes

Fang²,

Lu³

et al. 2022

Front. Immunol.

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ObjectiveThe purpose of the study is to evaluate the effects of anticardiolipin (aCL) and/or anti-β2-glycoprotein-I (aβ2GPI) antibodies, namely antiphospholipid antibodies (aPL), on in vitro fertilization (IVF) outcomes.Materials and methodsThe study group comprised infertile women with aPL undergoing IVF-ET cycles. Controls were infertile women with tubal etiology without aPL. The impact of aPL on reproductive outcomes, such as oocyte quality, embryo quality, and implantation capacity, was compared between the study group and controls. Additionally, peripheral blood T cell subsets, such as T helper (Th)1, Th2, Th17, and T regulatory (Treg) cells and cytokines, were analyzed by the flow cytometry. Differences between the study group and controls were analyzed.ResultsA total of 132 infertile women, including 44 women with aPL, and 88 controls were sequentially recruited for this study. Women with aPL had lower numbers of total and perfect/available embryos and lower rates of MII oocytes, blastocyst formation, perfect and available embryos, implantation, clinical pregnancy, and take-home baby. Additionally, imbalanced Th1/Th2 and Th17/Treg ratios, significantly higher levels of serum IL-2, TNF-α, IFN-γ, and IL-17A, and a significantly lower serum IL-4 were noticed in women with aPL compared to controls.ConclusionWomen with aPL such as aCL and/or aβ2GPI antibodies were associated with adverse IVF outcomes. Early screening for aPL and appropriate consultation for couples undergoing IVF should be considered. In addition, underlying immunopathology and inflammatory immune mechanisms associated with aPL should be further explored.

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Section: Discussionmentioning

confidence: 99%

Anticardiolipin and/or anti-β2-glycoprotein-I antibodies are associated with adverse IVF outcomes

Fang²,

Lu³

et al. 2022

Front. Immunol.

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“…Besides anti-clotting properties of the antithrombotic agents, such as aspirin and LMWH, their action on the T-cell peripheral blood profile is suggested. 23 The efficacy of these agents as a therapy of RM is debatable. 24,25 However, in women with persistent antiphospholipid antibodies, its usage increases the live birth rate.…”

Section: Isscuss I Onmentioning

confidence: 99%

“…Besides anti‐clotting properties of the antithrombotic agents, such as aspirin and LMWH, their action on the T‐cell peripheral blood profile is suggested 23 . The efficacy of these agents as a therapy of RM is debatable 24,25 .…”

Section: Disscussionmentioning

confidence: 99%

Unexplained recurrent miscarriages: predictive value of immune biomarkers and immunomodulatory therapies for live birth

Kolańska

Dabi

Dechartres

et al. 2021

American J Rep Immunol

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Introduction: Recurrent miscarriages are defined as three or more early miscarriages before 12 weeks of gestation. The aim of this study was to describe a cohort of women with unexplained recurrent miscarriages, evaluate several potential biomarkers of immune origin, and describe the outcome of pregnancies under immunomodulatory therapies.Methods: Women having a history of at least 3 early miscarriages without any etiology were recruited from 3 university hospitals.Results: Among 101 women with recurrent miscarriages, overall, 652 pregnancies have been included in the analysis. Women which experienced miscarriages were older (33.3 ± 5.4 versus 31.9 ± 6.7; p = 0.03), with history of more pregnancies (4 (2-6) versus 3.5(1-5.75); p 0.0008), and less frequently the same partner (406 (74%) versus 79 (86%); p=0.01). There was no difference in the level and frequencies of biomarkers of immune origin (NK, lymphocyte, gamma globulins and blood cytokine levels and endometrial uNK activation status), except the higher rates of positive antinuclear antibodies in women with live birth (12 (13%) versus 36 (7%); p=0.03). Among the 652 pregnancies, 215 (33%) have been treated and received either aspirin/low weighted molecular heparin (LMWH) and/or combined to different lines of immunomodulatory treatment.Patients with pregnancy under treatment had a significantly higher rate of cumulative live birth rate than those with untreated ones (43.0% vs 34.8%; p = 0.04). When compared to patients with untreated pregnancies, patients with steroids during the pregnancy had twice more chances to obtain live birth (OR 2.0, CI95% 1.1 -3.7, p = 0.02). Conclusions:Unexplained recurrent miscarriages could have improved obstetrical outcome under immunomodulatory therapies and in particular steroids.

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“…Th1 cytokines play an essential role in the development of diffuse proliferative lupus nephritis (DPLN), while Th2 cytokines play an essential role in the development of membranous lupus nephritis (MLN) [ 12 ]. Aspirin can effectively regulate the balance of Th1/Th2 cytokines [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Benefits of Hydroxychloroquine Combined with Low-Dose Aspirin on Pregnancy Outcomes and Serum Cytokines in Pregnant Women with Systemic Lupus Erythematosus

Zhang

et al. 2022

Drugs R D

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Background and Objective Systemic lupus erythematosus (SLE) is an autoimmune disease, with hydroxychloroquine being the main therapeutic agent for the treatment of SLE. This research explored the effects of hydroxychloroquine combined with low-dose aspirin on maternal and infant outcomes and cytokines of pregnant women with SLE. Methods Ninety pregnant women with SLE were divided into the hydroxychloroquine (HCQ) group (45 cases) and the hydroxychloroquine combined with low-dose aspirin (HCQASP) group (45 cases) by random number table. Patients in the HCQ group were treated with oral administration of hydroxychloroquine, while patients in the HCQASP group were treated with low-dose aspirin based on oral administration of hydroxychloroquine. Pregnancy outcomes, fetal outcomes, and cytokine levels were statistically analyzed. ResultsThe HCQASP group had a significantly higher proportion of full-term pregnancies and a significantly lower proportion of hypertension, prematurity, and pregnancy loss than the HCQ group. Neonates in the HCQASP group also had significantly higher birth weights and Apgar scores and a significantly lower proportion of neonatal asphyxia than the HCQ group. After treatment, the HCQASP group had significantly higher interleukin (IL-2) and interferon (IFN)-γ levels and significantly lower IL-4 and IL-10 levels than the HCQ group. Conclusion Hydroxychloroquine combined with low-dose aspirin can effectively improve the pregnancy outcomes of pregnant women with SLE by affecting the levels of T helper (Th) 2 and Th1 cytokines.

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Heparin and aspirin combination therapy restores T-cell phenotype in pregnant patients with antiphospholipid syndrome-related recurrent pregnancy loss

Cited by 11 publications

References 43 publications

Anticardiolipin and/or anti-β2-glycoprotein-I antibodies are associated with adverse IVF outcomes

Anticardiolipin and/or anti-β2-glycoprotein-I antibodies are associated with adverse IVF outcomes

Unexplained recurrent miscarriages: predictive value of immune biomarkers and immunomodulatory therapies for live birth

Benefits of Hydroxychloroquine Combined with Low-Dose Aspirin on Pregnancy Outcomes and Serum Cytokines in Pregnant Women with Systemic Lupus Erythematosus

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