BACKGROUND: Antiphospholipid syndrome (APS) is a multisystem disease that may present as venous or arterial thrombosis and/or pregnancy complications with the presence of antiphospholipid antibodies. Until today, heterogeneity of pathogenic mechanism fits well with various clinical manifestations. Moreover, previous studies have indicated that genes are differentially expressed between normal and in the disease state. Hence, this study systematically searched the literature on human gene expression that was differentially expressed in Obstetric APS.
METHODOLOGY: Electronic search was performed until 31st March 2015 through PubMed and Embase databases; where the following Medical Subject Heading (MeSH) terms were used and they had been specified as the primary focus of the articles; gene, antiphospholipid, obstetric, and pregnancy in the title or abstract. From 502 studies retrieved from the search, only original publications that had performed gene expression analyses of human placental tissue that reported on differentially expressed gene in pregnancies with Obstetric APS were included. Two reviewers independently scrutinized the titles and the abstracts before examining the eligibility of studies that met the inclusion criteria. For each study; diagnostic criteria for APS, method for analysis, and the gene signature were extracted independently by two reviewers. The genes listed were further analysed with the DAVID and the KEGG pathways.
RESULTS: Three eligible gene expression studies involving obstetric APS, comprising the datasets on gene expression, were identified. All three studies showed a reduction in transcript expression on PRL, STAT5, TF, DAF, ABCA1, and HBEGF in Obstetric APS. The high enrichment score for functionality in DAVID had been positive regulation of cell proliferation. Meanwhile, pertaining to the KEGG pathway, two pathways were associated with some of the listed genes, which were ErBb signalling pathway and JAK-STAT signalling pathway.
CONCLUSION: Ultimately, studies on a genetic level have the potential to provide new insights into the regulation and to widen the basis for identification of changes in the mechanism of Obstetric APS.
The presence of antiphospholipid antibodies (aPLs) is closely associated with thrombotic events and pregnancy complications such as recurrent pregnancy loss, preeclampsia and placental insufficiency. We investigated the presence of aPLs and its frequency among female patients with a history of fetal loss in a Malaysia population. Serum samples were collected from 108 patients who had (1) one or more unexplained deaths of morphologically normal fetuses at or beyond the 22nd week of gestation, or (2) one or more premature births of morphologically normal neonates at or before the 24th week of gestation due to eclampsia or preeclampsia, or recognized features of placental insufficiency, or (3) three or more unexplained, consecutive, spontaneous miscarriages before the 20th week of gestation. Serum was tested for aPLs subtypes: anticardiolipin (aCL), anti-beta-2- glycoprotein I (aβ2GPI), anti-beta-2-glycoprotein I dependent cardiolipin (aβ2GPI dependent CL), anti-phosphatidylcholine (aPC), anti-phosphatidylethanolamine (aPE), anti-phosphatidylinositol (aPI), anti-phosphatidylserine (aPS) and anti-sphingomyeline (aSph) by using the enzyme-linked immunosorbent assay (ELISA) method. The mean age of patients was 30±5. Four patients (3.7%) were found positive for at least one aPLs subtype. Four aPLs subtypes were detected. The most common subtypes was aβ2GPI dependent CL (3.7%), followed by aCL (2.7%), aβ2GPI (0.9%), and aPE(0.9%). In conclusion, frequency of aPLs among women with fetal loss (3.7%) in Malaysia was low with subtype aβ2GPI dependent CL being the most prevalent aPLs.
Insufficient experimental studies have reported the effect of ovalbumin (OVA) as an allergen towards embryonic growth in asthma mouse model. The impact of 10 μg/200 μL OVA on maternal inflammatory and oxidative stress (OS) responses, and preimplantation embryonic development was investigated in this study. We first established OVA-induced asthma mouse model, and following superovulation, mated the females and challenged them with Methacholine (Mch) test. Upon embryo retrieval, only those with the highest implantation potential were cultured in vitro. Significant reduction in the number of embryos at each preimplantation stage was noted in the treated group. Uneven sized blastomeres at 2-, 4- and 8-cell stages were also evident in this group. Embryo fragmentation was significant at only 2-, 4- and 8-cell stages. We also found that OVA tended to raise maternal inflammatory and OS biomarker levels as well as to cause inappropriate levels of pregnancy hormones progesterone (P4) and estrogen (E2) although insignificant. The combined results indicate that 10 μg/200 μL OVA had altered both quality and quantity of the embryos in asthma mouse model although its effect on pregnancy hormones, inflammatory and OS responses were non-pathological.
Serum concentrations of thyroid stimulating hormone (TSH) and thyroid autoantibodies in pregnant patients with thyroid disease at various stages of pregnancy were determined by in-house ELISAs. In normal pregnancy, serum TSH levels were significantly elevated (p < 0.05) from 13 weeks of gestation. The normal reference ranges for TSH for the second (0.6-5.0 mIU/l) and third trimester (0.6-5.6 mIU/l) were significantly higher (p < 0.05; p < 0.01 respectively) compared to 0.4-4.5 mIU/l for the first trimester. In pregnant thyroid patients, serum TSH levels correlated highly (p < 0.001) to T4 (r = 0.740), FT4I (r = 0.683) and MicAb (microsomal antibodies) (r = 0.825) but weaker (p < 0.01) to T3 (r = -0.512), FT3I (r = 0.520) and TgAb (thyroglobulin antibodies) (r = 0.618). Thus, measurement of TSH with the highly sensitive ELISA (enzyme linked immunosorbent assay) would form a useful first line test for thyroid dysfunction in pregnancy while measurement of thyroid autoantibodies would aid in the diagnosis of autoimmune hypothyroidism.
A pregnant woman with antiphospholipid syndrome presented with repeated venous thromboembolism (VTE) in the first and second trimesters of pregnancy despite receiving combination therapy with low-molecular-weight heparin and aspirin. The addition of hydroxychloroquine prevented further VTE recurrence, thus demonstrating its potential antithrombotic effects.
This study was undertaken to determine the presence of thyroid autoantibodies and associated pregnancy complications from 49 pregnant women with thyroid disease. There were 31 (63%) women with Graves' disease (GD) and 18 (37%) with primary hypothyroidism (PHT). A total of 26 (53.1%) women, 19 (61%) with GD and seven (39%) with PHT, had positive antibodies. Six had thyroid peroxidase antibodies (TPO), one with thyroglobulin antibody (TG) and eight had TSH receptor antibodies (TR). Two had a mixture of antibodies involving TG/TPO (one GD vs one PHT), four with TG/TPO/TR (all had GD) and five with TPO/TR (four with GD vs one with PHT). There were associations in women with positive thyroid antibodies and pre-eclampsia (15.4%), abruptio placenta (4%), caesarean deliveries (31%), postpartum thyroiditis (19.2%) and abnormal neonatal thyroid function (15.4%). Women with positive thyroid antibodies in pregnancy need close care during and after pregnancy, as they can develop complications affecting both mother and fetus.
This study aimed at investigating the maternal characteristics that in turn influence the immunological status of infants in asymptomatic enteric pathogen carriers in mother baby pairs (MBPs) in a high HIV burdened population in Harare, Zimbabwe. BIOPLEX immunoassay was used to analyse serum samples from 39 MBPs for 27 cytokines and 6 immunoglobulins. The MBP were purposively selected based on HIV infection and Entamoeba histolytica carriage. Logistic regression was used to identify any link between maternal demographic and clinical data with infant cytokine and immunoglobulin levels. Maternal E. histolytica carriers were more likely to have infants with low levels of IL-12p70, FGF-basic, GM-CSF and TNF-α cytokines (OR: 0.14; 95% CI: 0.03-0.79) and high levels of IgA immunoglobulin (OR: 8.1; 95% CI: 1.45-45.06). HIV infected mothers were more likely to have infants with low levels of IgG2 (OR: 0.24; 95% CI: 0.06-1.00) and IgA (OR: 0.22; 95% CI: 0.05-0.90) immunoglobulins. Notably, it was highly likely to deliver infants with low IgG4 levels (OR: 0.24; 95% CI: 0.06-1.02) for maternal mean age above 30.38 years (Standard deviation 6.09) though not significant (p=0.05). Maternal E. histolytica asymptomatic carriage, and HIV-infection status result in low levels of pro-inflammatory cytokines IL-12p70, FGF-basic, GM-CSF and TNF-α and immunoglobulins IgG2, IgG4 and IgA on their infants.