Correction: C-Peptide and leptin system in dichorionic, small and appropriate for gestational age twins-possible link to metabolic programming?

The original version of this Article was updated shortly after publication to correct two mistakes.Under Figure 2, "The results were recalculated accordingly: nanograms [ng] of studied protein per 100 µ" should read "The results were recalculated accordingly: picograms [pg] of studied protein per 100 µg".

C-Peptide and leptin system in dichorionic, small and appropriate for gestational age twins-possible link to metabolic programming?

Children born small for gestational age (SGA) are at increased risk of future glucose intolerance and type 2 diabetes, possibly after due intrauterine metabolic programming. Soluble leptin receptor (SLR) limits leptin access to signal-transducing membrane receptors. The present study examines whether SGA and appropriate for gestational age (AGA) twins differ with regard to their C-peptide, glucose and leptin systems. The markers C-peptide, glucose, fetal leptin, and SLR in cord blood were assessed in children from dichorionic twin pregnancies at delivery. In 32 cases, weight differed by >15% between twins: one demonstrated Intrauterine Growth Retardation (IUGR) (<10th percentile-SGA), while the other did not (AGAI). The other 67 pairs presented appropriate weight for gestational age (AGAII). Placental leptin and placental leptin receptor content were also assessed. Despite the same concentrations of glucose, the SGA twins maintained a higher level of C-peptide [44.48 pmol/l vs. 20.91 pmol/l, p < 0.05] than the AGAI co-twins, higher HOMA index, calculated as [C-peptide] x [Glucose] (p = 0.045), in cord blood, and a higher level of SLR [SGA vs AGAI-mean: 28.63 ng/ml vs. 19.91 ng/ml, p < 0.01], without any differences in total leptin (p = 0.37). However, SGA placentas demonstrated higher leptin level [130.1 pg/100 g total protein vs 83.8 pg/100 g total protein, p = 0.03], without differences in placental leptin receptor (p = 0.66). SGA/IUGR twins demonstrate relative insulin resistance accompanied by decreased fetal and increased placental leptin signaling. We speculate that relative insulin resistance and changes in the leptin system might be the first evidence of processes promoting deleterious metabolic programming for post-natal life.

[Current opinions on immunological processes in rheumatoid arthritis during pregnancy]. / Wspólczesne poglady na przebieg procesów immunologicznych w reumatoidalnym zapaleniu stawów u kobiet w ciazy.

The essential in pathogenesis of RA is induction of incorrect immunological response against synovial and connective tissue antigens, which depends of CD4+ T-cells activation by specific antigen. This stimulation leads to releasing Th1 lymphokines. The most important cytokine is TNF-alpha. An increased level of TNF-alpha, IL-1, IL-6, GM-CSF, IL-8 was observed in patients with RA. PDGF, FGF, TGF, C-X-C a chemokines (IL-GRO-alpha, ENA78) and CCb chemokines (RANTES, MCP1 MIP1 alpha) are also involved in synovial hyperplasia in RA. During a pregnancy a clinical improvement in women with RA is frequent. The reason of this fact is probably connected with Th2 predominance (IL-4, IL-10) caused by presence of fetal tissues. Specific, cell-mediated immunity is suppressed and changed to Th2 by progesterone and PGE2. During a pregnancy a higher sensitivity of lymphocytes to progesterone was found. Progesterone stimulates T cells to PIBF production, which decreases NK activity. Th2 cytokines (Il-6, IL-10, IL-13, TGF) are expressed on decidua and inhibit secretion of Th1 cytokines (IL-2, INF gamma, TNF-alpha, IL-1 alpha, IL-1 beta). Immunosuppression caused by pregnancy probably decreases inflammatory and destructive reactions in tissues women with RA. The first attack of this disease frequently observed during puerperium is connected with a high level of prolactin and a low of estrogens, which causes a increased release of IL-2 and has a main influence on initiation and increasing of inflammatory process in RA.

[The role of peripheral blood lymphocyte subpopulations in differentiation between preeclampsia and transient hypertension]. / Znaczenie oznaczen subpopulacji limfocytów krwi obwodowej w róznicowaniu pomiedzy preeklampsja a nadcisnieniem przemijajacym w ciazy.

OBJECTIVES: Hypertension is the most frequent complication of pregnancy after 24th week of gestation, occurring in 8% of pregnancies and being the main cause of perinatal mortality and morbidity. It is classified as preeclampsia (PE) or transient hypertension (TH). According to some statements PE and TH are distinct syndromes of different pathogenesis. There are even opinions emphasizing that in most cases TH is in fact undiagnosed chronic hypertension. The role of immunological system in pathogenesis of PE is well known but the hypothesis that immunological events are engaged in pathogenesis of chronic hypertension has not been proved so far. Assuming that TH is closer in its pathogenesis to chronic hypertension than to PE it would be possible to differentiate between TH and PE using some immunological tests. If PE and TH are the same, the differences would be insignificant. DESIGN: The aim of this study was to check the hypothesis that peripheral blood lymphocyte subsets analysis is an useful tool in differentiation between PE and TH and confirmation of their distinct origin. MATERIALS AND METHODS: The study groups consisted of 19 pregnant women with PE (mean age 25.5 +/- 2.5 years, mean gestational age 32.5 +/- 2.5 weeks, 84.2% primiparae) and 14 pregnant women with TH (mean age 27.0 +/- 3.0 years, mean gestational age 33.5 +/- 3.0 weeks, 100% primiparae) diagnosed between 30-37 week of gestation. All women were matched according to gestational age and race. They had no renal diseases or chronic hypertension prior to pregnancy neither had any features of them during the study. Exclusion criteria were: uterine contractions, infection and therapy with steroids before blood sampling. PE and TH were defined according to USA National Health Institute criteria. Peripheral blood was obtained by venipuncture. Standard immunofluorescent marking techniques for whole blood with one-step monoclonal antibodies were performed. Lymphocyte subsets (CD19+, CD3+, CD4+, CD8+, CD3-/CD16+/CD56+, CD3+/CD16+/CD56+, CD8+/CD28+, CD4+/CD45RA+, CD4+/CD45RO+, CD3+/CD69+) analysis was done with flow-cytometer FACSCalibur with 488 nm argon laser. The lymphocyte cells region was chosen with LeucoGATE and analysis performed with SimulSET v.3.1 programme. Statistical analysis was based on Student T test. RESULTS: The differences in peripheral blood lymphocyte subsets composition between PE and TH were insignificant. CONCLUSION: Is that on the basis of peripheral blood lymphocyte subsets analysis PE and TH despite different clinical symptoms seem to have common pathogenesis. However there is possibility that changes observed in peripheral blood are not significantly different in PE and TH because of their low importance for immunopathogenesis.

[The role of cytokines in Th1/Th2 balance in pregnant women with transient hypertension]. / Rola wybranych cytokin w równowadze Th1/Th2 u ciezarnych z nadcisnieniem przemijajacym w ciazy (NP).

OBJECTIVES: There is growing evidence that Th1/Th2 imbalance in cytokine network may play role in immunopathology of preeclampsia (PE). Normal pregnancy is "Th2 phenomenon" while PE is believed to be caused by Th1-shift. There is few data concerning Th1/Th2 imbalance in transient hypertension of pregnancy (TH). DESIGN: The aim of this study was to check the hypothesis that changes in IFN-gamma and IL-2 (Th1 cytokines) levels are accompanied with deficit in TGF-beta (anti-Th1 cytokine) production in TH. MATERIALS AND METHODS: The study group consisted of 10 pregnant women with TH diagnosed between 30-37 week of gestation (mean age 27.0 +/- 3.0 years, mean gestational age 33.5 +/- 3.0 weeks) and 10 women with uncomplicated pregnancy (mean age 26.0 +/- 3.5 years, mean gestational age 35.5 +/- 1.5 weeks). All women were primigravidae matched according to gestational age and race. They had no diabetes mellitus and renal diseases prior to pregnancy neither had any features of them during the study. They had no hypertension before pregnancy. Exclusion criteria were: uterine contractions, infection and therapy with steroids before blood sampling. TH was defined according to USA National Health Institute criteria. Peripheral blood lymphocytes (PBL) were cultured for 72 hours in standard 1640 RPMI medium enriched with 20% FCS, L-glutamine, antibiotics (Sigma) and mitogen phytohemaglutynine (PHA) (Sigma). Cytokine levels were estimated in culture supernatants by using standard ELISA kits according to the indications of the producer (R&D). Statistical analysis was performed with Student-T test. RESULTS: In TH group the levels of IL-2 were higher compared with control group but the differences did not reach statistical significance (4.5 vs. 1.56 pg/ml, t = -1.00, p < 0.1). The same referred to IFN-gamma levels (754.0 vs. 771.0 pg/ml, t = -0.04, NS). However, TGF-beta levels were significantly lower in TH group compared with control group (2459.2 vs. 4156.4 pg/ml, t = -1.47, p < 0.05). Conclusion is that there is a significant deficit of TGF-beta production in peripheral blood lymphocytes of women with TH studied "in vitro". This may contribute to Th1-shift seen in TH similarly to PE.

IL-12, IL-6 and IFN-gamma production by lymphocytes of pregnant women with rheumatoid arthritis remission during pregnancy.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease with progressive activity. The RA remission was observed in women during pregnancy, but the mechanism responsible for remission is hypothetical only and concerns mechanisms of immune regulation such as lymphocyte subpopulations and interleukin production. AIMS: The lymphocyte subpopulations and interleukin production in vitro in a group of healthy non-pregnant women, healthy pregnant women and pregnant women suffering from RA may help towards a better understanding of regulation of the immune processes. METHODS: The investigations were performed in trimester III--2 days after delivery and 6 weeks after delivery. Peripheral blood lymphocytes were isolated on Gradisol gradient and analysed immediately or after having been cultured for 72 hours in RPMI medium supplemented with 10% FCS. The cultures were terminated after 72 h, supernatants stored at -72 degrees C for interleukin evaluation. The concentrations of IFN-gamma, IL-2, IL-6, IL-12, TNF-alpha and its soluble receptors R-I, R-II were estimated in non-stimulated and PHA (Sigma, 5 microg/ml) stimulated culture supernatants using ELISA Endogen kits according to the manufacturer's instructions. RESULTS: The general pattern of T cell subpopulation distribution was similar in all analysed groups. Decreased IFN-gamma, IL-12 and increased IL-6 production by lymphocytes after PHA stimulation was found in trimester III in pregnant women with RA as compared to healthy pregnant woman. CONCLUSION: The obtained results suggest that in pregnant women with RA the TH1 cell response predominates, contrary to healthy pregnant women with TH2 type functional response. These phenomena were not observed after delivery.