COVID-19 in patients with anemia and haematological malignancies: risk factors, clinical guidelines, and emerging therapeutic approaches.

Extensive research in countries with high sociodemographic indices (SDIs) to date has shown that coronavirus disease 2019 (COVID-19) may be directly associated with more severe outcomes among patients living with haematological disorders and malignancies (HDMs). Because individuals with moderate to severe immunodeficiency are likely to undergo persistent infections, shed virus particles for prolonged periods, and lack an inflammatory or abortive phase, this represents an overall risk of morbidity and mortality from COVID-19. In cases suffering from HDMs, further investigation is needed to achieve a better understanding of triviruses and a group of related variants in patients with anemia and HDMs, as well as their treatment through vaccines, drugs, and other methods. Against this background, the present study aimed to delineate the relationship between HDMs and the novel COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Besides, effective treatment options for HDM cases were further explored to address this epidemic and its variants. Therefore, learning about how COVID-19 manifests in these patients, along with exploiting the most appropriate treatments, may lead to the development of treatment and care strategies by clinicians and researchers to help patients recover faster. Video Abstract.

Apoptotic activity of Newcastle disease virus in comparison with nisin A in MDA-MB-231 cell line.

Given the development of drug-resistant cancer cells, designing alternative approaches for cancer treatment seems essential. In this study, we evaluated the anti-tumor effects of nisin A and Newcastle disease virus (NDV) on triple-negative MDA-MB-231 cell line. The MDA-MB-231 cell line was separately and in combination subjected to the different concentrations of a Vero-adapted NDV (JF820294.1) and nisin A. The oncolytic effects of these treatments were analyzed by different cytotoxic and apoptosis techniques including trypan blue staining, MTT assay, acridine orange (EB/AO) staining, colony assay and flow cytometry over time. Nisin A at doses of more than 20.00 µg mL-1 could represent the anti-viral effects and interfere with the oncolytic activity of NDV. Moreover, the analyses indicated that the anti-proliferative and cytotoxic features of combination therapy were stronger than those of individual NDV groups. However, the most apoptotic effect was seen in NDV experimental groups. Taken together, the results from cytotoxicity tests, flow cytometry and colony assay showed that either of the oncolytic agents had significant effects at low concentrations 72 hr post-treatment. Thereby, they had the potential to be used as new approaches in cancer treatment.

Association of Human Leukocyte Antigen Alleles with Carbamazepine- or Lamotrigine-Induced Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in an Iranian Population: A Case-control Study.

Background: Genetic diversity in human leukocyte antigen (HLA) alleles across populations is a significant risk factor for drug-induced severe cutaneous adverse reactions (SCARs), e.g., carbamazepine (CBZ)- and lamotrigine (LTG)-induced Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). The present study aimed to investigate the frequency of different HLA alleles in Iranian patients with CBZ- and LTG-induced SJS/TEN. Methods: A case-control study was conducted from 2011 to 2018 at various hospitals affiliated with Shiraz University of Medical Sciences (Shiraz, Iran). A total of 31 patients receiving anticonvulsant drugs (CZB or LTG) were recruited and divided into two groups. The drug-induced group (n=14) included hospitalized patients due to CBZ- or LTG-induced SJS/TEN. The drug-tolerant group (n=17) included individuals receiving CBZ or LTG for at least three months with no adverse effects. In addition, 46 healthy individuals (control group) were recruited. The frequency of HLA-A, -B, and -DRB1 alleles in patients with CZB- or LTG-induced SJS/TEN was investigated. HLA typing was performed using the allele-specific polymerase chain reaction method. The Chi square test and Fisher's exact test were used to determine a potential association between SJS/TEN and HLA alleles. P<0.05 was considered statistically significant. Results: CBZ- or LTG-induced SJS/TEN was not significantly associated with HLA alleles. However, HLA-DRB1*01 showed a significantly higher frequency in patients with CBZ-induced SJS/TEN than the CBZ-tolerant patients (30% vs. 9%, P=0.07). Conclusion: Overall, no significant association was found between CBZ- or LTG-induced SJS/TEN and HLA alleles. Further large-scale studies are required to substantiate our findings.

Alteration in IFN-γ and CCL2 serum levels at first trimester of pregnancy contribute to development of preeclampsia and fetal growth restriction.

OBJECTIVE: Pregnancy is a unique challenge for the immune system. Any disturbance in the immune system in the first trimester could result in further pregnancy complications. In this regard, the current study aimed to investigate the association between serum levels of a group of cytokines in the first trimester of pregnancy with the onset of preeclampsia (PE) and fetal growth restriction (FGR). MATERIALS AND METHODS: Serum samples were collected from 550 pregnant women at their 11th - 13th weeks of pregnancy and followed up to delivery. Out of all cases, 15 women complicated with preeclampsia and 15 ones diagnosed with FGR were included in the study. The serum levels of IFN-γ, CCL2, IL-10, IL-35 and IL-27 were checked in the collected sera of mentioned patients and compared to 60 women with normal pregnancy outcomes. RESULTS: In the preeclampsia group, the mean level of IFN-γ was significantly higher (p < 0.001) while the CCL2 serum level was significantly lower (p < 0.003) as compared to control group. There was no significant difference between the preeclampsia group and controls regarding other cytokines. In the FGR group, the mean serum level of IFN-γ was significantly higher compared to the healthy pregnancy group (p < 0.001) but other cytokines showed no significant differences. In the FGR group, a significant positive correlation was found between IL-10 level and neonates' weight (p < 0.05). CONCLUSION: Based on the results of the present study, an elevated level of IFN-γ and a reduced level of CCL2 at the first trimester of pregnancy could lead to complications such as PE and/or FGR.

Association between gene polymorphisms of IL-12, IL-12 receptor and IL-27 and organ involvement in Iranian endometriosis patients.

Endometriosis is an inflammatory disease characterized by the presence of ectopic endometrial tissue, immune cell dysfunction and abnormal cytokine secretion. In addition to immunological factors, genetic variations that influence endometriosis severity and cytokine expression levels play important roles in the pathogenesis of this disease. Interleukin-12 (IL-12), specifically its p40 subunit encoded by IL-12B gene and the interleukin-12 receptor ß1 (IL-12Rß2) chain of its receptor, as well as interleukin-27 (IL-27) are important in the establishment of endometriosis. So, in this study, we measured IL-12 and IL-27 serum levels and investigated the possible links between IL-12B rs3212227, IL-12Rß2 rs3790565 and IL-27 rs153109 polymorphisms and the risk of developing endometriosis in a group of Iranian women. In this case-control study, 162 endometriosis patients and 151 healthy women were included and tested for the aforementioned polymorphisms using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The enzyme-linked immunosorbent assay (ELISA) method was also used to measure IL-12 and IL-27 serum levels. Although there was no statistically significant association between the genotypes and alleles of the studied polymorphisms and the development of endometriosis in general, the AA genotype of IL-12B rs3212227 showed a significant association with uterine endometriosis when compared to AC+CC genotypes (p = .04, CI = 0.270-0.988, OR = 0.517). Indeed, the AA genotype of the IL-12B rs3212227 single nucleotide polymorphism (SNP) may be linked with a lower risk of developing uterine endometriosis. There was no significant difference in IL-27 levels between the two studied groups (p = .49), and IL-12 levels were undetectable in both groups. In conclusion, the AA genotype of IL-12B rs3212227 might be associated with a decreased risk of uterine involvement in endometriosis patients.

In vitro-Generated MDSCs Reduce the Pregnancy Complications in an Abortion-Prone Murine Model.

Recurrent spontaneous abortion (RSA) is one of the major pregnancy-related complications. The roles of different immune cells have been studied in pregnancy complications. The current study aimed to investigate myeloid-derived suppressor cells (MDSCs) in a murine abortion model and introduce a therapeutic approach by using in vitro-generated MDSCs in this model. CBA/J × DBA/2 (abortion prone) and CBA/J × Balb/C (normal pregnancy) mice were used. The frequency of granulocytic MDSCs, monocytic MDSCs, and Tregs was checked in the bone marrow and uteroplacental tissue of mice on three gestational days (gd9.5, gd13.5, and gd17.5) using the flow cytometry approach. MDSCs were generated in vitro from bone marrow-isolated cells using GM-CSF and IL-6 cytokines. Abortion-prone mice were injected intravenously with in vitro-generated MDSCs at gd0.5, and pregnancy outcomes were recorded in treated mice. The frequency of G-MDSCs and M-MDSCs in the bone marrow of abortion-prone mice was decreased at gd9.5 (p = 0.026 and p = 0.05, respectively). In uteroplacental tissue, the frequency of G-MDSCs was significantly lower at gd9.5 and gd13.5 (p = 0.001, p = 0.029, respectively), while M-MDSCs only showed decreased number at gd9.5 (p = 0.05) in abortion-prone mice. Injection of in vitro-generated MDSCs resulted in the increased fetus and placenta weights (p = 0.049 and p = 0.012, respectively) but showed no effect on the number of live fetuses and abortion rate. The reduced frequency of both G-MDSCs and M-MDSCs in the bone marrow and at the feto-maternal interface is associated with pregnancy complications. In vitro-generated MDSCs could be considered as a potential approach to reduce these complications.

Are genetic variations in IL-1ß and IL-6 cytokines associated with the risk of pre-eclampsia? Evidence from a systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis study was performed to assess the potential association between interleukin-1 beta (IL-1ß) single nucleotide polymorphisms (SNPs) (rs1143634 and rs16944) and interleukin-6 (IL-6) SNP (rs1800795) and pre-eclampsia (PE). METHODS: A comprehensive literature search was conducted in the international search engines and databases, including MEDLINE (via PubMed), Scopus, and Web of Science (ISI) up to 9 March 2021. After retrieving relevant articles, data extraction was performed by four authors independently. Pooled ORs and corresponding 95% CIs were used to evaluate the association between IL-1ß and IL-6 polymorphisms and PE risk. Cochran's Q test was used to check heterogeneity, and the I2 index was calculated for measuring the heterogeneity between the estimations of included studies. RESULTS: After reviewing fully published studies, 21 studies were included in this study based on the eligibility criteria. Our results showed that rs16944 and rs1143634 of IL-1ß were significantly associated with the risk of PE. Regarding rs16944, the minor C allele significantly decreased the risk of PE (C vs. T: OR = 0.79, 95% CI = 0.69-0.90). In contrast, the minor T allele of rs1143634 significantly increased the risk of PE (T vs. C: OR = 1. 28, 95% CI = 1.04-1.58). There was no significant association between IL-6 rs1800795 (C vs. G: OR = 1.04, 95% CI = 0.93-1.16) polymorphism and PE risk. CONCLUSIONS: In conclusion, this meta-analysis suggests rs1143634 and rs16944 polymorphisms of IL-1ß are related to the risk of PE.

Investigating the Association between IL-27 and Susceptibility to Preeclampsia among Iranian Women.

BACKGROUND: Preeclampsia (PE) is one of the most serious disorders of human pregnancy with a high rate of mortality for the fetus and mother. Several etiological factors are involved in the onset of this disease. Upregulation of IL-27 has been reported in placental tissue recovered from preeclamptic women, but the role of IL-27 has not yet been investigated in PE. The aim of the study was to investigate the association of IL-27 rs153109 and rs17855750 gene polymorphisms with PE; also, protein levels and susceptibility and severity of PE in Iranian women were evaluated. METHODS: This case-control study was performed on 199 PE patients and 228 healthy women as the control group. IL-27 rs153109 and rs17855750 SNPs were genotyped using a PCR-RFLP method. Moreover, the levels of IL-27 were determined in 40 PE and 45 healthy women using ELISA method. RESULTS: Statistical analysis indicated that there were no differences in genotype, allele and genotype combination frequencies in the SNPs between cases and controls. The plasma level of IL-27 was elevated in the mild form of the disease compared with controls (p-value: 0.006). CONCLUSIONS: The effect of IL-27 in preeclampsia is not due to the studied cytokine polymorphisms, but the level of IL-27 might be associated with the severity of preeclampsia in Iranian women.

Association between interleukin-32 gene polymorphism and susceptibility to preeclampsia.

OBJECTIVE: To determine association between IL-32 gene polymorphism, and serum levels of IL-32 and susceptibility to preeclampsia (PE). METHODS: The frequency of IL-32 rs9927163 and rs4786370 polymorphisms was determined by PCR-RFLP. Also ELISA was used to determine the levels of serum IL-32. RESULTS: Regarding rs4786370 C/T SNPs, the frequencies of CT, TT genotypes, and T allele were shown to be higher in the PE patients. IL-32 serum level significantly increased in the PE patients. CONCLUSION: Variety of allele and genotype IL32 rs4786370 as well as a rise in serum level of IL-32 can be regarded as a risk factor for PE.

Evaluation of Transforming Growth Factor-ß1 and Interleukin-35 Serum Levels in Patients with Placenta Accreta.

OBJECTIVE: Placenta accreta is a pregnancy-related disorder with extreme trophoblast invasion and the adherence of the placenta to the uterine wall. This study aimed to investigate the serum level of transforming growth factor-beta 1 (TGF-ß1) and interleukin (IL)-35 in patients with placenta accreta. METHODS: Thirty-one women with placenta accreta and 57 healthy pregnant women were enrolled. The serum levels of TGF-ß1 and IL-35 were measured using the enzyme-linked immunosorbent assay method. RESULTS: The serum levels of both TGF-ß and IL-35 were significantly higher in the placenta accreta group compared with the group of healthy women (1082.48 pg/mL vs 497.33 pg/mL and 4541.14 pg/mL vs 1306.04 pg/mL; P <.001, respectively). Moreover, the level of TGF-ß1 positively correlated with the IL-35 level but other factors such as age, gestations, live births, and abortions did not correlate with IL-35 and TGF-ß1 levels. CONCLUSION: The serum levels of IL-35 and TGF-ß1 may contribute to the pathogenesis of placenta accreta and could be considered as potential targets in clinical and diagnostic approaches.

T Cell Proliferative Responses and IgG Antibodies to ß2GPI in Patients with Diabetes and Atherosclerosis.

BACKGROUND: Diabetes increases the risk of myocardial infarction (MI) by 2 to 3 folds. Tlymphocytes play a role in atherosclerosis, which is the main pathology behind MI. Cellular immune responses to beta-2 glycoprotein I (ß2GPI) are shown in carotid atherosclerosis. OBJECTIVE: To investigate the self-reactive, ß2GPI-specific T-lymphocytes in patients with and without diabetes and atherosclerosis. METHODS: Collectively, 164 subjects with and without diabetes that underwent coronary angiography were divided into four groups based on their diabetes status and coronary stenosis. Group I=Diabetic with ≥50% stenosis: A+D+ (n=66); Group II=Non-diabetic with ≥50% stenosis, A+D- (n=39); Group III=Diabetic with <50% stenosis: A-D+ (n=28); and Group IV=Non-diabetic with <50% stenosis: AD- (n=31). All groups were evaluated for anti-ß2GPI IgG antibody by ELISA method. Then, PBMCs were isolated from 18 subjects and were stimulated with ß2GPI-derived peptides to assess their proliferation in accordance with their HLA-DRB1 alleles. RESULTS: Mean ß2GPI IgG levels were higher in groups with ≥50% stenosis (A+) compared to those with <50% stenosis (A-), (P=0.02). The co-presence of diabetes in A+ individuals increased mean ß2GPI-specific IgG. Auto-reactive ß2GPI-specific T cells were detected in the repertoire of T-lymphocytes in all groups. ß2GPI-peptides showed promiscuous restriction by various HLADRB1. CONCLUSION: ß2GPI is the target of cellular and humoral immune responses in patients with atherosclerosis. Since the T cell responses but not antibodies were detectable in A-D+ and A-D- groups, it is reasonable to assume that cellular responses preceded the humoral responses. Post-translation modifications of ß2GPI under oxidative and glycemic stresses may have increased the IgG levels in patients with diabetes. Finally, identification of antigens that trigger immuno-pathogenesis in atherosclerosis and diabetes may help the development of immunomodulation methods to prevent or treat these debilitating diseases.

Proteome Analysis of CD4+ T Cells Reveals Differentially Expressed Proteins in Infertile Polycystic Ovary Syndrome Patients.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most frequent endocrine disorder affecting 6-7% of premenopausal women. Recent studies revealed that the immune system, especially CD4+ T helper cells are important in the context PCOS. Proteome analysis of CD4+ T lymphocytes can provide valuable information regarding the biology of these cells in the context of PCOS. OBJECTIVE: To investigate immune dysregulation in CD4+ T lymphocytes at the protein level in the context of PCOS using two-dimensional gel electrophoresis (2DE) and mass spectrometry (MS). METHODS: In the present study, we applied two-dimensional gel electrophoresis / mass spectrometry to identify proteins differentially expressed by peripheral blood CD4+ T cells in ten PCOS women compared with ten healthy women. Western blot technique was used to confirm the identified proteins. RESULTS: Despite the overall proteome similarities, there were significant differences in the expression of seven spots between the two groups (P <0.05). Three proteins, namely phosphatidylethanolaminebinding protein 1, proteasome activator complex subunit 1 and triosephosphate isomerase 1 were successfully identified by Mass technique and confirmed by western blot. All characterized proteins were over-expressed in CD4+ T cells from patients compared to CD4+ T cells from controls (P <0.05). Insilico analysis suggested that the over-expressed proteins interact with other proteins involved in cellular metabolism, especially glycolysis and ferroptosis pathway. CONCLUSION: These findings suggest that metabolic adjustments in CD4+ T lymphocytes, which is in favor of increased glycolysis and Th2 differentiation are important in the context of PCOS.

Response Comment on "Association between Interleukin-32 and Interleukin-17A Single Nucleotide Polymorphisms and Serum Levels with Polycystic Ovary Syndrome".

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Seminal plasma and CD4+ T-cell cytokine profiles in the in vitro fertilization success.

BACKGROUND: Abnormal female immune response is one of the potential causes of unexplained infertility (UI). Seminal plasma (SP) is an important regulator of female immune responses during pregnancy. This study investigated a SP effect on the expression of CD4+ T-cell-related cytokines in a group of UI woman candidates for in vitro fertilization (IVF) and healthy fertile women. MATERIALS AND METHODS: This was a semi-experimental study that performed on 20 UI couples (ten unsuccessful and ten successful IVF outcomes) and 10 fertile couples as the healthy group. CD4+ T-cells were separated from peripheral blood mononuclear cells of women by magnetic-activated cell sorting technique and incubated with (stimulated condition) or without (unstimulated condition) SP of their husbands. After incubation, real-time polymerase chain reaction method was used to investigate interleukin (IL)-23, IL-17, IL-4, IL-10, transforming growth factor (TGF)-ß, and interferon (IFN)-γ gene expression. Mann-Whitney U-test, Kruskal-Wallis test, and Wilcoxon signed-rank test were used for statistical analysis. RESULTS: Baseline TCD4+ mRNA levels of IL-23 (P = 0.03) and TGF-ß (P = 0.01) were different between healthy and infertile groups. However, IL-17, IL-4, IFN-γ, and IL-10 were expressed similarly regardless of fertility status. Comparing mRNA expression before and after SP exposure, our results have shown that relative expression of IL-23 significantly increased in successful (P = 0.04) and unsuccessful IVF groups (P = 0.01), whereas IL-10 expression increased only in the IVF failure group (P = 0.01). CONCLUSION: SP can make a positive effect on IVF outcome through alteration in CD4 + T-cell-related cytokines expression, especially IL-10 and IL-23.

Stereological study of the placental structure in abortion-prone mice model (CBA/J×DBA/2J).

Recurrent spontaneous abortion (RSA) is an important reproductive health issue defined as the loss of two or more consecutive pregnancies before the 20th week of gestation, affecting 2-5% of couples. This study aimed to evaluate the volume, number of cells, and length of the vessels in the placenta in normal and abortion-prone (AP) pregnant mice on gestational day (gd) 13.5. Fetal and placental tissues of female CBA/J mated DBA/2J (AP group) and BALB/c (normal pregnant group) were collected and prepared for stereological assessments on gd13.5. The volumes of the placenta and its main layers decidua basalis (Db), junctional zone (Jz), and labyrinth zone (Lz) were investigated. The number of spongiotrophoblast cells, glycogen cells, giant cells, trophoblast cells, lymphocytes, and neutrophils were estimated as well. The AP group showed a reduction in the volume of the placenta (48.7%) and its components. Moreover, the number of spongiotrophoblast cells (66.7%), glycogen cells (76.2%), giant cells (73.3%), and trophoblast cells (81.4%) was decreased in AP compared to normal pregnant (NP) mice. Also, in AP group recognized a 10-fold increase in the number of lymphocytes and a four-fold increase in the number of neutrophils in comparison to the NP group (p < 0.05). Activation of different immune cell types might induce systemic inflammation at the feto-maternal interface, resulting in impaired placenta formation and abortion.

Analysis of the frequency of type 2 innate lymphoid cells and regulatory T cells in abortion-prone mice.

Recurrent spontaneous abortion (RSA) is the most common pregnancy related complication, affecting 1-5 % of pregnancies. Despite hormonal, genetic and anatomical factors that result in abortion, impairment of immune response at the feto-maternal interface during the first trimester of pregnancy is also one of the main causes of RSA. In the present study, we evaluated the frequency of blood and uterine group 2 innate lymphoid cells (ILC2s), their subsets and regulatory T cells (Tregs) in CBA/J × DBA/2 J as an abortion-prone model compared to normal pregnant (NP) mice using immunophenotyping. Results indicated that the percentages of ILC2s were significantly decreased in the AP group compared to the NP group at mid-gestation (P ≤ 0.01). Moreover, the percentages of both blood and uterine nILC2s were increased in NP mice at mid-gestation (P ≤ 0.01, and P ≤ 0.05, respectively), while iILC2s significantly increased in AP mice at mid-gestation (P ≤ 0.01, and P ≤ 0.05, respectively). Tregs were reduced in AP mice at both early and mid-gestation stages (P ≤ 0.01). Overall, our findings suggest that the changes in blood and uterine ILC2s might be associated with abortion in mice.

MDSCs in pregnancy: Critical players for a balanced immune system at the feto-maternal interface.

Myeloid-derived suppressor cells (MDSCs) have emerged as a new immune regulator at the feto-maternal interface. Although the phenotypes and functions of these cells were primarily studied in pathological conditions such as cancers and infections, new evidence has underscored their beneficial roles in homeostasis and physiological circumstances such as normal pregnancy. In this regard, studies have shown an increased number of MDSCs, particularly granulocytic MDSCs, at the feto-maternal interface. These cells participate in maintaining immunological tolerance between mother and semi-allograft fetus through various mechanisms. They further seem to play critical roles in placentation and fetus growth process. The absence or dysregulation of MDSCs during pregnancy have been reported in several pregnancy complications. These cells are also abundant in the cord blood of neonates so as to balance the immune responses and prevent aggressive inflammatory responses. The current review summarizes and organizes detailed data on MDSCs and their roles during pregnancy.

Analysis of the frequencies and functions of CD4+CD25+CD127low/neg, CD4+HLA-G+, and CD8+HLA-G+ regulatory T cells in pre-eclampsia.

Most of the investigations on regulatory T cells (Treg) have focused on CD4+CD25+Foxp3+ Treg cells. Although new subsets of these cells such as CD4+CD25+CD127low/neg, CD4+HLA-G+, and CD8+HLA-G+ Treg cells have been introduced, documents regarding these populations are limited or controversial in case of pregnancy and pre-eclampsia (PE). Here, we investigated the frequencies of the three aforementioned Treg cell subsets in the peripheral blood of non-pregnant (n = 15), healthy pregnant, and preeclamptic women (n = 17 in each group) using flow cytometry. We also assessed the ability of the isolated CD4+CD25+CD127low/neg and CD4+HLA-G+ Treg cells to suppress responder T cells proliferation and cytokine secretion using CFSE dye dilution and ELISA technique. Our results showed that the frequency of CD4+CD25+CD127low/neg Treg cells was significantly lower in preeclamptic women (p =  0.001). Also, this subset negatively correlated with both systolic (R= - 0.401, p =  0.004) and diastolic (R= - 0.541, p =  0.001) blood pressures. Regarding CD4+HLA-G+ and CD8+HLA-G+ Treg cells, the mean percentages of these cells were significantly higher in the context of normal pregnancy (p <  0.01). Finally, our results in the functional assay experiments did not show statistically significant differences between groups (p ≥  0.05), but they reveal a shift toward the lower suppressive capacity of CD4+CD25+CD127low/neg and CD4+HLA-G+ Treg cells in preeclamptic patients which might be clinically important. In conclusion, a significant decrease in the frequency of Treg cell subsets and also a shift toward the lower suppressive capacity of these cells in preeclamptic patients may lead to immunological maladaptation in the context of PE.

Serum and Peritoneal Fluid Cytokine Profiles in Infertile Women with Endometriosis.

BACKGROUND: Endometriosis is a chronic inflammatory disease with the growth of endometrial cells out of uterus and in the peritoneal cavity. T cell subsets participate in the establishment and progress of the disease by producing different cytokines. OBJECTIVE: To investigate a group of cytokines related to Th1/Th2/Th17/Treg subsets within both peripheral blood and peritoneal fluid (PF) samples from infertile endometriosis women. METHODS: Peripheral blood and PF samples were collected from 30 infertile endometriosis and 30 non-endometriosis fertile women during laparoscopy. Concentration of cytokines, including TNF-α, IFN-γ, TGF-ß1, IL-4, IL-10, IL-17 and IL-23 were evaluated using ELISA method. RESULTS: Results indicated that the concentration of IFN-γ within serum was significantly reduced in endometriosis group (p=0.001). Regarding PF cytokines, TGF-ß1 was increased in endometriosis group (p=0.030). Furthermore, the ratios of IFN-γ/TGF-ß1 and IL-17/IL-23 were significantly different between endometriosis and non-endometriosis women in serum samples (p<0.001 and p<0.01 respectively). The ratios of TNF-α/IL-10 and IL-17/IL-10 were also significantly different regarding PF samples between the two studied groups (p<0.04 and p<0.03 respectively). Finally, significant correlations were observed between the levels of IL-17 and IL-23, inflammatory and anti-inflammatory cytokines, in both samples and serum to PF inflammatory cytokines. CONCLUSION: Based on the results of the present study, in women with endometriosis, the disturbance of cytokines network might gradually activate the inflammatory responses and tissue repair, resulting in endometriosis development after several years.

T Cell Subsets Profiling in Unexplained Infertile Women with Successful and Unsuccessful in Vitro Fertilization Outcome: Focus on the Effect of Seminal Plasma.

Unexplained infertility (UI) is one of the most common diagnoses in the fertility care. Seminal plasma (SP) plays a crucial role in the regulation of female immune responses and the success of a pregnancy. In vitro fertilization (IVF) is a well-known method for the treatment of UI. In this study, we aimed to investigate the effect of SP on the differentiation of T helper (Th) cell subsets and the relationship between these subsets with the rate of IVF success in a group of women complicated with UI compared to those with normal pregnancy. This study was conducted on 20 UI couples (ten with successful and ten with unsuccessful IVF outcome) and 10 fertile couples as the control group. Four color flow cytometry technique was used to detect Th cell subsets in the peripheral blood mononuclear cells (PBMC) with or without stimulation by SP. Results indicated that the frequencies of IL-17+ and Foxp3+ T cells after incubation with SP was significantly increased in couples with unsuccessful IVF outcome as compared to successful and healthy groups (p<0.05). Additionally, a positive correlation was observed between Th1 and Th2 cells in the unsuccessful IVF group (R=0.6, p=0.03). In summary, the results of the present study demonstrated that exposure to SP might increase Th17 and Treg cell frequencies in infertile women with unsuccessful IVF, and might also balance inflammatory to regulatory responses to finally tune-up the Th1/Th2/Th17/Treg balance and support the success of IVF.