Altered Levels of Natural Autoantibodies against Heat Shock Proteins in Pregnant Women with Hashimoto's Thyroiditis.

The function of natural autoantibodies (nAAbs) in maintaining immunological tolerance has been comprehensively explained; however, their function in pregnant patients dealing with autoimmune diseases has not been thoroughly investigated. As Hashimoto's thyroiditis (HT) is the predominant organ-specific autoimmune condition of women of childbearing age, this study's objective was to evaluate IgM and IgG nAAbs targeting mitochondrial citrate synthase (CS) and heat shock proteins (Hsp60 and Hsp70) in women diagnosed with HT who were pregnant (HTP). Serum samples collected from HTP and healthy pregnant (HP) women in the first and third trimesters were tested using in-house-developed enzyme-linked immunosorbent assays (ELISAs). Our findings indicate the stability of nAAbs against CS and Hsps throughout the pregnancies of both healthy women and those with HT. However, during both trimesters, HTP patients displayed elevated levels of IgM isotype nAAbs against Hsp60 and Hsp70 compared to HP women, suggesting a regulatory role of IgM nAAbs during the pregnancies of patients with HT. Nonetheless, levels of IgG isotype nAAbs against Hsps were lower solely in the third trimester among HTP patients, resulting in a higher IgM/IgG ratio, which indicates their importance in alterations of the nAAb network during pregnancy in patients with HT.

Physiological Changes in the Levels of Anti-Cytokine Autoantibodies in Early Pregnancy Are Missing in Pregnant Women with Hashimoto's Thyroiditis.

T helper type 1 (Th1) and inflammatory cytokines play essential roles in early pregnancy and also in the pathogenesis of Hashimoto's thyroiditis (HT). Changes in the serum level of autoantibodies to cytokines, which may be able to modulate their availability and actions have been described in several autoimmune disorders. Yet, no data are available on anti-cytokine autoantibodies either during early pregnancy or in patients with HT. The aim of the study was to measure autoantibodies to inflammatory-, Th1- and Th22-cytokines in serum samples in healthy pregnancy (HP) and in pregnant women with HT (HTP). As pathological autoantibodies are hallmarks of HT, in addition we also measured anti-B-cell activator factor (BAFF) autoantibodies. The measurement was carried out with a Luminex multiplex assay and the Luminex MAGPIX Instrument, age-matched healthy women (HC) and women with HT (HT) were used as controls. In the first trimester of HP, anti-TNFα, anti-IL-8, and anti-IFNγ autoantibodies were significantly decreased, while autoantibodies to BAFF were significantly elevated compared to the HC. However, these alterations were not present in the HTP. Moreover, the levels of autoantibodies to IL-22 and TNFα were significantly increased in HTP compared to the HP. All differences in the levels of the investigated autoantibodies could be detected in the first trimester of pregnancies except for anti-IL-22 autoantibodies. According to our results we can conclude that alterations in the levels of autoantibodies to inflammatory and Th1 cytokines are physiological in the first trimester of pregnancy and their disturbance can be associated with autoimmune conditions such as HT.

The possible role of CD8+/Vα7.2+/CD161++ T (MAIT) and CD8+/Vα7.2+/CD161lo T (MAIT-like) cells in the pathogenesis of early-onset pre-eclampsia.

PROBLEM: The objective of this study was to compare the expressions of different immune-checkpoint molecules by MAIT and MAIT-like cells in healthy pregnancy and in early-onset pre-eclampsia. METHOD OF STUDY: Peripheral blood mononuclear cells (PBMC) were stained with monoclonal antibodies to characterize MAIT and MAIT-like cells. Flow cytometric analyses were used to measure PD-1, TIM-3, activation markers, and intracellular perforin expression. RESULTS: We identified CD3+/CD8+/Vα7.2+/CD161++ MAIT cells and a minor cell population characterized by CD3+/CD8+/Vα7.2+/CD161lo surface markers. In measuring the expression of PD-1 receptor, we found a significantly lower expression by MAIT cells in women with early-onset pre-eclampsia. CD69 expression by MAIT cells was significantly elevated in early-onset pre-eclamptic patients. Intracellular perforin content by MAIT and PD-1+ MAIT cells was significantly increased in pre-eclamptic patients compared with healthy individuals. CONCLUSION: Altered frequency and reduced PD-1 expression combined together with the elevated perforin content of MAIT cells insinuate their potential roles in the pathogenesis of early-onset pre-eclampsia.

Preliminary study of the effects of furosemide on blood pressure during late-onset pre-eclampsia in patients with high cardiac output.

OBJECTIVE: To examine the effect of furosemide on hypertension and edema in patients with pre-eclampsia experiencing high cardiac output. METHODS: The present cohort study enrolled patients with pre-eclampsia who were admitted to the pregnancy pathology unit of the Department of Obstetrics and Gynecology, University of Pécs, Hungary, between January 1 and December 31, 2015. Eligible patients had singleton pregnancies with no fetal anomalies, high blood volume, visible edema, and a hematocrit concentration below 37 L/L. Blood pressure was measured and impedance cardiography was used to determine cardiac output for all patients before they received a 40-mg dose of furosemide; after 60 minutes blood pressure and cardiac output were measured again. RESULTS: The study enrolled 14 patients. Lower cardiac output (P=0.002), systolic blood pressure (P=0.002), and diastolic blood pressure (P=0.002) were recorded after furosemide administration, with patient heart rates remaining stable. CONCLUSION: The heart-rate stability suggests that the change of cardiac output was due to a decrease in blood volume. These data suggest that diuretics could be useful in the management of late-onset pre-eclampsia, indicating that an increase in water retention could play a role in the development of late-onset pre-eclampsia.

Impact of maternal obesity on the fetal electrocardiogram during labor.

OBJECTIVE: Maternal obesity affects one in every five women giving birth worldwide. This condition is associated with adverse perinatal outcomes, as well as increased morbidity and mortality for mother and offspring. METHODS: We carried out a prospective study at the University of Pecs Medical Center, Pecs, Hungary, between 1 January 2013 and 1 January 2014. We enrolled 60 obese (body mass index >30 kg/m(2)) low-risk pregnant women and 108 age-, ethnicity-, and parity-matched nonobese pregnant control subjects. The ST segment of the fetal electrocardiogram was assessed by STAN® monitoring. Neonatal outcomes and cord gas analysis of the umbilical vessels were evaluated after birth. RESULTS: No infant with definitive metabolic acidosis was delivered in either group. We observed 32 and 106 ST events in the obese and control group, respectively, but this difference was not statistically significant. To date, none of the infants delivered as part of this study have demonstrated developmental insufficiency. CONCLUSIONS: Obesity might not influence the fetal electrocardiogram during labor as an independent risk factor for adverse pregnancy outcomes. Studies with larger cohort sizes are needed to confirm our findings.

L-arginine metabolism in early-onset and late-onset pre-eclamptic pregnancies.

OBJECTIVE: The present case-control study was undertaken to investigate l-arginine metabolism in pregnant women with early-onset and late-onset pre-eclampsia. Attempts were made to differentiate these two distinct diseases entities by using measured and derived parameters of l-arginine metabolism. STUDY DESIGN: Thirty-six patients with early-onset, 17 patients with late-onset pre-eclampsia and 15 healthy pregnant women at term were studied. Patients were categorized according to the weeks of gestation (< 34 vs. ≥ 34) at the appearance of clinical symptoms (hypertension + proteinuria). Venous samples were taken at gestational age of 29.8 ± 2.5, 36.1 ± 2.2 and 39.2 ± 1.2 weeks, respectively. L-arginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), monomethylarginine (MMA) and l-ornithine were measured by LC-MS/MS method. L-arginine/ADMA, l-ornithine/l-arginine, ADMA/SDMA ratios and the arginine methylation index (arg-MI) were calculated. RESULTS: Plasma levels of ADMA and MMA were significantly higher (p < 0.002) in pre-eclamptic patients than in healthy women. No significant differences could be detected between patients with early-onset and late-onset pre-eclampsia in either parameter studied. L-ornithine correlated positively with ADMA (r = 0.526, p < 0.001) and MMA (r = 0.533, p < 0.001) in the whole study population, and inversely with l-arginine (r = - 0.277, p < 0.044) in the pre-eclamptic group. When compared with maternal plasma in venous cord blood l-arginine was markedly reduced (p < 0.05) and there was a significant elevation in ADMA, SDMA, MMA and l-ornithine (p < 0.001, for each) without discernible differences between the study groups. CONCLUSIONS: Parameters of l-arginine metabolism do not discriminate the early-onset from late-onset pre-eclampsia. Our study provided indirect evidences for the redirection of l-arginine-NOS to the l-arginine-arginase pathway.