Genetic variation in C-reactive protein (CRP) gene is associated with retinopathy and hypertension in adolescents with type 1 diabetes.

BACKGROUND AND AIMS: Elevated concentration of CRP has been associated with the risk of diabetes as well as cardiovascular events and microvascular complications in T1D patients. We hypothesize that the +1846 C > T CRP gene polymorphism may have impact on the risk of T1D and/or its complications. METHODS: We have examined 400 young patients with T1D and 250 healthy age-matched controls. The +1846 C > T CRP gene polymorphism was genotyped by ARMS-PCR method. The analysis covers microvascular complications, concentrations of serum pro- and anti-inflammatory markers, adhesion molecules, proangiogenic factor as well as blood pressure. RESULTS: CT genotype (OR = 1.799) and T allele (OR = 1.733) are associated with increased risk of T1D, while CC genotype decreases the risk of this condition (OR = 0.458). Moreover, increased risk of hypertension corresponds with TT and T variant (OR = 3.116 and OR = 1.830, resp.) while CC genotype is decreasing the risk (OR = 0.547). Furthermore, CT variant is connected with lower risk of retinopathy (OR = 0.512) whereas TT variant decreases the risk of this complication (OR = 2.228). Our data also implies various effects of CRP +1846 C > T polymorphism on the inflammatory status of T1D patients. CONCLUSIONS: Although further studies are required, the +1846 C > T CRP gene polymorphism could be considered a genetic marker to predict susceptibility to retinopathy and hypertension in T1D adolescents.

Podocytes-The Most Vulnerable Renal Cells in Preeclampsia.

Preeclampsia (PE) is a disorder that affects 3-5% of normal pregnancies. It was believed for a long time that the kidney, similarly to all vessels in the whole system, only sustained endothelial damage. The current knowledge gives rise to a presumption that the main role in the development of proteinuria is played by damage to the podocytes and their slit diaphragm. The podocyte damage mechanism in preeclampsia is connected to free VEGF and nitric oxide (NO) deficiency, and an increased concentration of endothelin-1 and oxidative stress. From national cohort studies, we know that women who had preeclampsia in at least one pregnancy carried five times the risk of developing end-stage renal disease (ESRD) when compared to women with physiological pregnancies. The focal segmental glomerulosclerosis (FSGS) is the dominant histopathological lesion in women with a history of PE. The kidney's podocytes are not subject to replacement or proliferation. Podocyte depletion exceeding 20% resulted in FSGS, which is a reason for the later development of ESRD. In this review, we present the mechanism of kidney (especially podocytes) injury in preeclampsia. We try to explain how this damage affects further changes in the morphology and function of the kidneys after pregnancy.

Autoimmunity and Cancer-Two Sides of the Same Coin.

Autoimmune disease results from the immune response against self-antigens, while cancer develops when the immune system does not respond to malignant cells. Thus, for years, autoimmunity and cancer have been considered as two separate fields of research that do not have a lot in common. However, the discovery of immune checkpoints and the development of anti-cancer drugs targeting PD-1 (programmed cell death receptor 1) and CTLA-4 (cytotoxic T lymphocyte antigen 4) pathways proved that studying autoimmune diseases can be extremely helpful in the development of novel anti-cancer drugs. Therefore, autoimmunity and cancer seem to be just two sides of the same coin. In the current review, we broadly discuss how various regulatory cell populations, effector molecules, genetic predisposition, and environmental factors contribute to the loss of self-tolerance in autoimmunity or tolerance induction to cancer. With the current paper, we also aim to convince the readers that the pathways involved in cancer and autoimmune disease development consist of similar molecular players working in opposite directions. Therefore, a deep understanding of the two sides of immune tolerance is crucial for the proper designing of novel and selective immunotherapies.

Perinatal and neonatal outcome in patients with preeclampsia.

OBJECTIVES: Preeclampsia (PE) affects 2-5% of pregnant women. Hypertensive disorders of pregnancy are associated with adverse maternal and perinatal outcomes. MATERIAL AND METHODS: This study included 88 women showing gestational hypertension (GH) or PE symptoms, and their newborns. RESULTS: The rate of FGR was 43% for mothers with PE, compared to 8% with GH. The association was significant, p = < 0.001 but with moderate strength, Cramer's V = 0.40. The risk of FGR increased nine times when PE occurred, as the odds ratio was 9.25 (CI: 2.46-34.83), p = 0.001. PE was associated with FGR risk if delivery time was less than 34 weeks compared to a delivery time of more than 34 weeks. This was 82% of FGR cases for < 34 weeks, compared with 35% of cases in > 34 group, (p = 0.001; Cramer's V = 0.50). PE was also associated (p = 0.01, Cramer's V = 0.27) with the type of delivery, as the caesarean section rate was 74%, compared to 50% in the GH group. This made it three times higher the likelihood of delivery by caesarean section, as the odds ratio was 3.10 (CI: 1.24-7.75), p=0,02. Delivery time was significantly (p < 0.001) shortened to 38 weeks (27-41), compared to 40 weeks (38-42) GH mothers. There was no distinction in median age for PE and GH mothers (p = 0.124). The overall clinical status of neonates was proportional despite the mother's PE. The sum of Apgar points in the first, and then the second to third minute, did not differ significantly, p = 0.370 and 0.560, respectively. The number of peripheral blood platelets and leucocytes was not reduced (p = 0.821 and 0.534) in infants when the mother suffered from PE. CONCLUSIONS: The prediction of adverse maternal outcomes from hypertensive diseases of pregnancy is key to optimal management, including the timing of delivery and planning for the most appropriate place of care.

Cytokine Imprint in Preeclampsia.

The hallmark of preeclampsia (PE) is a shift toward persistent inflammatory response, accompanied by endothelial dysfunction. The driving forces in PE are proinflammatory cytokine and growth factors, in parallel with reduced functionality of anti-inflammatory effectors, like regulatory T cells are observed. Unfortunately, no conclusive mechanism underlying preeclampsia has been identified. For this reason, research on preeclampsia is needed to provide a state of the art understanding of the pathophysiology, identification of new diagnostics tools and the development of targeted therapies. The 68 patients were divided into three groups: gestational hypertension (GH) group (n = 19) and PE group (n = 28) and a control group (n = 21). We have tested a set of 53 cytokines, chemokines and growth factors in preeclampsia and gestational hypertension, and then compared them with normal pregnancies. Using a diagnostic test assessment characteristic parameters (IL-22, MDC/CCL22, IL-2/IL-4 ratio) have been identified and cut-off values have been proposed to diagnose preeclampsia. All parameters had high negative or positive predictive values, above 80%. In conclusion, we have proposed a potential set of immune parameters to diagnose preeclampsia.

Comparisons of Dipstick Test, Urine Protein-to-Creatine Ratio, and Total Protein Measurement for the Diagnosis of Preeclampsia.

Preeclampsia affects 2-5% of pregnant women and is one of the leading causes of maternal and perinatal morbidity and mortality. We aimed to extensively evaluate proteinuria in women with preeclampsia and to determine the analytical sensitivity and specificity of and the cutoff values for urine protein-to-creatinine ratio (UPCR) and total protein in 24 h urine samples. This study included 88 women. We used the urine dipstick test, UPCR, and total protein measurement in a 24 h urine sample. The patients were divided in gestational hypertension (GH, n = 44) and preeclampsia (PE, n = 44) groups. In the GH group, 25% (11/44) of the patients presented incidentally positive results. UPCR and total protein in 24 h urine specimens were increased in the GH group compared to the PE group. Receiver operating characteristic analysis showed a UPCR cutoff of 30 mg/mmol as significant for preeclampsia, while the sensitivity and specificity were 89% (95% CI, 75-97) and 100% (95% CI, 87-100), respectively. In the 24 h urine protein test, sensitivity and specificity were 80% (95% CI, 61-92) and 100% (95% CI, 88-100), respectively, for the cutoff value of 0.26 g/24 h. In comparison to the other commonly used tests here considered, UPCR determination is a reliable, relatively faster, and equally accurate method for the quantitation of proteinuria, correlates well with 24 h urine protein estimations, and could be used as an alternative to the 24 h proteinuria test for the diagnosis of preeclampsia.