scholarly journals The Complement System, T Cell Response, and Cytokine Shift in Normotensive versus Pre-Eclamptic and Lupus Pregnancy

2021 ◽  
Vol 10 (24) ◽  
pp. 5722
Author(s):  
Eugen Ancuța ◽  
Radu Zamfir ◽  
Gabriel Martinescu ◽  
Dragoș Valentin Crauciuc ◽  
Codrina Ancuța
Keyword(s):  
T Cell Response ◽  
Inflammatory Factor ◽  
Hypertensive Disorder ◽  
Vascular Events ◽  
Complement Inhibitors ◽  
Vasoactive Factors ◽  
Th2 Polarization ◽  
Immune Alterations ◽  
Autoimmune Conditions ◽  
Normotensive Pregnancy

Successful pregnancy requires an immunological shift with T helper CD4+ bias based on disbalance Th1/Th17 versus Th2/T regulatory (Tregs) required to induce tolerance against the semi-allogeneic fetus and placenta and to support fetal growth. Considered a pregnancy-specific hypertensive disorder, pre-eclampsia is characterized by multifaceted organ involvement related to impaired maternal immune tolerance to paternal antigens triggered by hypoxic placental injury as well as excessive local and systemic anti-angiogenic and inflammatory factor synthesis. Both systemic and local Th1/Th2 shift further expands to Th17 cells and their cytokines (IL-17) complemented by suppressive Treg and Th2 cytokines (IL-10, IL-4); alterations in Th17 and Tregs cause hypertension during pregnancy throughout vasoactive factors and endothelial dysfunction, providing an explanatory link between immunological and vascular events in the pathobiology of pre-eclamptic pregnancy. Apart from immunological changes representative of normotensive pregnancy, lupus pregnancy is generally defined by higher serum pro-inflammatory cytokines, lower Th2 polarization, defective and lower number of Tregs, potential blockade of complement inhibitors by anti-phospholipid antibodies, and similar immune alterations to those seen in pre-eclampsia. The current review underpins the immune mechanisms of pre-eclampsia focusing on local (placental) and systemic (maternal) aberrant adaptive and innate immune response versus normotensive pregnancy and pregnancy in systemic autoimmune conditions, particularly lupus.

scholarly journals A comparative study of the serum levels of antiphospholipid antibodies in hypertensive disorder of pregnancy and normotensive pregnancy

2017 ◽  
Vol 6 (2) ◽  
pp. 580
Author(s):  
Guljit Kaur ◽  
Sangeeta Pahwa ◽  
Amanbeer Kaur ◽  
Madhu Nagpal
Keyword(s):  
Antiphospholipid Antibodies ◽  
Serum Levels ◽  
Phosphatidyl Serine ◽  
Hypertensive Disorder ◽  
Blood Samples ◽  
Glycoprotein I ◽  
History Of ◽  
Hypertensive Disorder Of Pregnancy ◽  
Normotensive Pregnancy ◽  
In Pregnancy

Background: Antiphospholipid antibodies have been associated with a number of obstetric complications however their role in the pathogenesis of preeclampsia has remained uncertain Therefore, the utility of screening for antiphospholipid antibodies among women at risk for recurrent hypertensive disorder of pregnancy is still doubtful. This study is aimed to clarify relationship between hypertensive pregnancies and APLA.Methods: A prospective, randomized was conducted and, 120 patients after 20 weeks of gestation were studied. 60 patients had hypertensive disorder in pregnancy and 60 were normotensive. Blood samples were obtained from them under all asepsis, serum was separated and tested for Antiphospholipid antibodies (Anticardiolipin, anti beta 2 glycoprotein I, phosphatidyl -serine, -inositol, -ethanolamin, -choline and sphingomyelin and lupus anticoagulant), apart from other routine investigations using Aeskulsia Phospholipid-Screen-GM.Results: 4/60 and 3/60 hypertensive patients had raised IgM and IgG levels respectively. Their values came in equivocal range. 2 of the normotensive patients had equivocal range values of both IgM/IgG. Mean of IgM APLA in hypertensive and normotensive patients was 2.54 and 1.67 respectively and difference between these values was statistically non significant (p=0.081). Mean of APTT is similarly statistically non significant in two groups (p=0.817).Conclusions: No significant correlation between the hypertensive state in pregnancy and antiphospholipid antibodies, hence this test should not be recommended as a screening test in pregnancies and there was no need to assess these antibodies in the hypertensive cases of pregnancy without the history of thrombosis or autoimmune diseases.

scholarly journals CCR5 and CXCR3 Are Dispensable for Liver Infiltration, but CCR5 Protects against Virus-Induced T-Cell-Mediated Hepatic Steatosis

2007 ◽  
Vol 81 (18) ◽  
pp. 10101-10112 ◽  
Author(s):  
P. J. Holst ◽  
C. Orskov ◽  
K. Qvortrup ◽  
J. P. Christensen ◽  
A. R. Thomsen
Keyword(s):  
T Cell ◽  
Chemokine Receptors ◽  
Intervention Studies ◽  
Viral Infections ◽  
T Cell Response ◽  
Effector Cells ◽  
Virus Control ◽  
Autoimmune Conditions ◽  
Considerable Controversy ◽  
Chemokine Ligands

ABSTRACT CCR5 and CXCR3 are important molecules in regulating the migration of activated lymphocytes. Thus, the majority of tissue-infiltrating T cells found in the context of autoimmune conditions and viral infections express CCR5 and CXCR3, and the principal chemokine ligands are expressed within inflamed tissues. Accordingly, intervention studies have pointed to nonredundant roles of these receptors in models of allograft rejection, viral infection, and autoimmunity. In spite of this, considerable controversy exists, with many studies failing to support a role for CCR5 or CXCR3 in disease pathogenesis. One possible explanation is that different chemokine receptors may take over in the absence of any individual receptor, thus rendering individual receptors redundant. We have attempted to address this issue by analyzing CCR5−/−, CXCR3−/−, and CCR5/CXCR3−/− mice with regard to virus-induced liver inflammation, generation and recruitment of effector cells, virus control, and immunopathology. Our results indicate that CCR5 and CXCR3 are largely dispensable for tissue infiltration and virus control. In contrast, the T-cell response is accelerated in CCR5−/− and CCR5/CXCR3−/− mice and the absence of CCR5 is associated with the induction of CD8+ T-cell-mediated immunopathology consisting of marked hepatic microvesicular steatosis.

Abstract 3: Preeclampsia-induced T Helper-associated Cytokine Imbalances Persist Postpartum

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Sabrina M Scroggins ◽  
Gabrielle Gray ◽  
Cassandra Berkey ◽  
Robin E Gandley ◽  
Elizabeth F Sutton ◽  
...  
Keyword(s):  
Future Development ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Tissue Bank ◽  
Fetal Tissue ◽  
Hypertensive Disorder ◽  
T Helper ◽  
The Future ◽  
Anti Inflammatory ◽  
Normotensive Pregnancy

Preeclampsia (PreE), a hypertensive disorder in pregnancy, contributes to long-term maternal cardiovascular disease risk. By 2025, it is estimated that more women than men will have hypertension (HTN), yet the mechanisms contributing to the development of HTN in women are less understood. One potential mechanism underlying HTN in women is a persistent imbalance of anti- and pro- inflammatory T H cells following PreE. Consistent with this, anti-inflammatory T helper (T H ) cytokines are reduced and pro-inflammatory T H cytokines are increased during a PreE pregnancy. De-identified and coded plasma samples and clinical data were obtained from the Magee-Women’s Research Institute & Foundation or the University of Iowa Maternal-Fetal Tissue Bank (IRB 201808705) from women 1-3 (N=93) or 8-10 (N=58) years (yrs) following a normotensive (CTL) or PreE-affected pregnancy. Postpartum (PP) HTN was defined as having stage 1 or higher HTN as designated in the updated 2017 ACC/AHA guidelines. Women with PreE had higher rates of HTN at 1-3 years and at 8-10 years PP, (24% vs. 5% and 65% vs. 17%, all p<0.05) compared to women with a normotensive pregnancy. To determine if T H cells play a role in the future development of HTN, we investigated if the T H cytokine changes observed in PreE persist 1-3 yrs and 8-10 yrs PP. Cytokine concentrations were determined via ELISAs and normalized to total protein. Average cytokine concentrations are reported in pg/g. At 1-3 yrs PP, concentrations of anti-inflammatory cytokines IL-4 (47 vs. 6819, p<0.05), IL-10 (1204 vs. 15042, p<0.05) and TGFβ (8.2x10 5 vs. 4.4x10 6 , p<0.05) were reduced in women with a prior PreE pregnancy vs. women with a CTL pregnancy. At 8-10 yrs PP, pro-inflammatory IL-6 (86 vs. 18, p<0.05) and TNFα (298 vs. 53, p<0.05) were both significantly increased in women with prior PreE compared to women with a CTL pregnancy. Here, we confirm women with a prior PreE pregnancy present with a higher prevalence of HTN early (1-3 yrs) and later (8-10 yrs) PP compared to women with a normotensive pregnancy. Further, we show an altered T H cytokine milieu persists following delivery in women with PreE. This pro-inflammatory milieu is associated with increased rates of HTN and thus, may underlie the future development of HTN in women with a history of PreE.

scholarly journals P1251THROMBIN GENERATION ASSAY: A POTENTIAL TOOL TO STRATIFY THROMBOTIC RISK IN HEMODIALYSIS PATIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Ileana Kalikatzaros ◽  
Massimo Radin ◽  
Irene Cecchi ◽  
Savino Sciascia ◽  
Giacomo Forneris ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Venous Thrombosis ◽  
Thrombin Generation ◽  
Previous History ◽  
International Normalized Ratio ◽  
Vascular Events ◽  
Thrombotic Risk ◽  
Thrombin Generation Assay ◽  
Autoimmune Conditions ◽  
History Of

Abstract Background and Aims Patients with Chronic Kidney Disease (CKD) in hemodialysis (HD) show both high thrombotic and hemorrhagic risks. However, routine laboratory techniques aimed to evaluate haemostasis, i.e. activated prothrombin time (PT) and activated partial thromboplastin time (aPTT), are not sensitive enough to detect mild hypocoagulable or hypercoagulable states in this population. Indeed, these methods evaluate the start-up phase of the coagulation, but omit the amplification stage in which an exponential increase of thrombin generation occurs. Thrombin generation assay (TGA) is a second-level global coagulative test able to evaluate thrombin generation and decay. So far the TGA has never been used for assessing thrombotic risk in HD patients. Method This is a monocentric observational retrospective study conducted at San Giovanni Bosco Hospital and University of Turin, Italy. After chart-reviewing of all patients with CKD in HD, we enrolled: Group A) 100 Patients with CKD in HD, treated or not treated with warfarin Group B) 60 Patients treated with Warfarin with normal kidney function Group C) 60 Healthy Controls Results Compared to healthy donor patients on hemodialysis that were not treated with warfarin had significantly lower tLag (mean tLag 8.2±3.4 vs. 9.7±2.9, p &lt; 0.05), lower tPeak (mean tPeak 14.3±6 vs. 16.2±4.7, p &lt; 0.05), lower Peak (mean Peak 151.8±77.4 vs. 209.2±103.8, p &lt; 0.001) and lower AUC (mean AUC 1624.5±564.4 vs. 2023±489.2, p &lt; 0.001) (Figure 1). Compared to controls with normal renal function treated with warfarin, HD patients treated with warfarin had higher tLag (mean tLag 10.5±3.3 vs. 8.3±2.1, p &lt; 0.05), higher tPeak (mean tPeak 16.5±4.9 vs. 13±2.9, p &lt; 0.05). Among HD patients who were not treated with warfarin, those with autoimmune conditions showed a pro-thrombotic TGA profile when compared to HD patients without autoimmune diseases, with significantly higher Peak (mean Peak 188.4±30 vs. 149.9±78.7, p &lt; 0.05) and higher AUC (mean AUC 2066.9±138.2 vs. 1601.5±569, p &lt; 0.001). Similarly, compared to patients without previous history of vascular events (59), patients with previous ischemic stroke or venous thrombosis (41), had significantly lower tLag (mean tLag 8±2.9 vs. 14.2±8.5, p &lt; 0.001), lower tPeak (mean tPeak 14±5.6 vs. 21.7±12.3, p &lt;0.05), higher Peak (mean Peak 154.9±76.8 vs. 71.83±49.2, p&lt;0.05) and higher AUC (mean AUC 1653.7±548.7 vs. 863.4±501.4, p &lt; 0.05). Of note, a significant positive relationship was detected between the International Normalized Ratio (INR) and both tLag (Pearson 0.46, p &lt;0.001) and tPeak (Pearson 0.35, p &lt;0.001). INR was inversely correlated to Peak (Pearson -0.47, p &lt;0.001) and AUC (Pearson -0.61, p &lt;0.001) (Figure 2). Conclusion Identifying patients at high risk for cardiovascular diseases and thrombosis has an important impact on the management of patients with CKD in HD. In this study, we observed a prothrombotic TGA profile in patients with CKD in HD, especially those with autoimmune conditions or previous history of arterial events (especially ischemic stroke) or venous thrombosis. Prospective studies are needed to evaluate the possible clinical use of TGA as thrombotic risk stratification tool in HD patients.

“Aspirin - resistance”? A few critical considerations on definition, terminology, diagnosis, clinical value, natural course of atherosclerotic disease, and therapeutic consequences

VASA ◽  
2011 ◽  
Vol 40 (6) ◽  
pp. 429-438 ◽  
Author(s):  
Berent ◽  
Sinzinger
Keyword(s):  
Platelet Function ◽  
Point Of Care ◽  
Aspirin Resistance ◽  
Point Of View ◽  
Evidence Based ◽  
Platelet Function Tests ◽  
Clinical Value ◽  
Vascular Events ◽  
Therapeutic Consequences ◽  
Function Tests

Based upon various platelet function tests and the fact that patients experience vascular events despite taking acetylsalicylic acid (ASA or aspirin), it has been suggested that patients may become resistant to the action of this pharmacological compound. However, the term “aspirin resistance” was created almost two decades ago but is still not defined. Platelet function tests are not standardized, providing conflicting information and cut-off values are arbitrarily set. Intertest comparison reveals low agreement. Even point of care tests have been introduced before appropriate validation. Inflammation may activate platelets, co-medication(s) may interfere significantly with aspirin action on platelets. Platelet function and Cox-inhibition are only some of the effects of aspirin on haemostatic regulation. One single test is not reliable to identify an altered response. Therefore, it may be more appropriate to speak about “treatment failure” to aspirin therapy than using the term “aspirin resistance”. There is no evidence based justification from either the laboratory or the clinical point of view for platelet function testing in patients taking aspirin as well as from an economic standpoint. Until evidence based data from controlled studies will be available the term “aspirin resistance” should not be further used. A more robust monitoring of factors resulting in cardiovascular events such as inflammation is recommended.

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