A Well-Intentioned Enemy in Autoimmune and Autoinflammatory Diseases: NETosis.

Neutrophils are an essential member of the innate immune system derived from the myeloid stem cell series and develop in the bone marrow. The action of neutrophils defined in immune response includes phagocytosis, degranulation, cytokine production, and neutrophil extracellular traps. The success of the host immune defense depends on effective neutrophil activation. Recent studies have shown that neutrophils that have completed their task in the field of inflammation rejoin circulation. Uncontrolled inflammatory response and dysregulated immune responses to the host are important factors in the development of acute and chronic diseases. Neutrophils are the first cells to be drawn into the field at the time of inflammation. They have developed response strategies that produce proinflammatory cytokines and are known as neutrophil extracellular traps since they create mesh-like structures with their DNA contents into the external environment and release their granular proteins in this way. This article summarizes numerous recent studies and reviews the role of neutrophil extracellular traps in autoimmune and autoinflammatory diseases in the hope, that this will lead to the development of more effective treatments. In addition, in this review, the role of neutrophil extracellular trap formation in some pediatric autoimmune diseases is emphasized.

Effects of smoking on the bone alkaline phosphatase in peri-implant crevicular fluid and implant stability quotient around implants before loading.

We aimed to examine the implant stability quotient (ISQ), alveolar bone level measurements (ABL), and bone alkaline phosphatase (BALP) in peri-implant crevicular fluid (PICF) around implants in smokers and non-smokers before loading in 3 months. 44 dental implants were placed into smoker and non-smoker patients equally. ISQ was measured at baseline and 3 months after surgery. The levels of PICF BALP and alveolar bone were measured. ISQ values significantly increased in smokers and non-smokers in the 3rd month (p < 0.05). ABL measurements were lower at 3 months compared to baseline in both groups (p < 0.05). Although ISQ and ABL values were higher in non-smokers than smokers at 3 months, the difference between the groups did not show any statistical significance. The PICF BALP levels in the 3rd month changed in both groups. But, these differences were insignificant. Although some of the measurements presented differences between the groups during the assessment periods, they were not indicative of the hazardous effects of smoking on bone healing around implants after surgery till functional loading in 3 months. However, smoking is an important factor to be considered for osseo-integration outcomes. Further studies are needed to clarify the influence of smoking on osseo-integration.

Evaluation of Plasma Urokinase-Type Plasminogen Activator Receptor (UPAR) in Patients With Chronic Hepatitis B, C and Non-Alcoholic Fatty Liver Disease (NAFLD) as Serological Fibrosis Marker.

BACKGROUND/AIMS: Progressive hepatic fibrosis is the main predictor of outcome and prognosis in chronic liver diseases. The importance of the coagulation cascade has been defined in liver fibrosis; however, the role of the fibrinolytic pathway has not been clear yet. We aimed to evaluate the association between the plasma levels of soluble urokinase Plasminogen Activator Receptor (uPAR) and the severity of liver fibrosis in chronic hepatitis B, C and Non-Alcoholic Fatty Liver Disease (NAFLD). METHODS: 96 chronic hepatitis B, 22 chronic hepatitis C and 11 NAFLD patients together with 47 healthy controls were enrolled in the study. uPAR plasma levels were detected by Enzyme-Linked Immunosorbent Assay (ELISA) method. RESULTS: The plasma levels of uPAR in patients with chronic hepatitis B and C significantly exceeded those of healthy controls (P < 0.001) while mean uPAR levels in patients with NAFLD were not different from healthy controls. Mean uPAR levels in chronic viral hepatitis patients with F1-F3 fibrosis and F4-F6 fibrosis were higher than those of control group (P < 0.001). Mean uPAR level in patients with F4-F6 fibrosis was significantly higher than that of patients with F1-F3 fibrosis (P < 0.001). CONCLUSION: This is the first study that investigated uPAR as a fibrosis marker in NAFLD and chronic hepatitis B patients. It is suggested that plasma levels of uPAR are closely related to the fibrosis stage in chronic hepatitis B and C and that uPAR might be a noninvasive marker of liver fibrosis.

Evaluation of serum procollagen C-proteinase enhancer 1 level as a fibrosis marker in patients with chronic hepatitis B.

AIM: Although liver biopsy has long been considered the gold standard for staging fibrosis, because of the disadvantages and risks of biopsy, several noninvasive processes such as serum biomarkers have been introduced for the assessment of liver fibrosis. The aim of this study was to assess the diagnostic value of serum procollagen C-proteinase enhancer 1 (PCPE-1) as a noninvasive fibrosis marker in treatment-naive chronic hepatitis B patients. PATIENTS AND METHODS: This study included 126 patients with biopsy-proven hepatitis B and 50 healthy controls. Fibrosis stage was determined using the Ishak scoring system. The PCPE-1 level was measured using the enzyme-linked immunosorbent assay assay, and the aspartate aminotransferase to platelet ratio index and the FIB-4 index were calculated using the formulas described in Appendix 1 (Supplemental digital content 1, http://links.lww.com/EJGH/A277). RESULTS: Serum PCPE-1 levels of chronic hepatitis B patients were found to be significantly lower than those of the healthy control group (4.49±2.74 vs. 42.9±59.6 pg/ml, respectively, P<0.001). There was a statistically significant negative correlation between serum PCPE-1 level and fibrosis stage (P=0.011; r=-0.226). A statistically significant negative correlation was found between serum PCPE-1 level and necroinflammatory activity (P=0.030; r=-0.194). PCPE-1 levels of patients with liver fibrosis scores of F1-2 were statistically significantly lower than those of the healthy control group (P<0.001) (area under the receiver operating characteristic: 0.955). The area under the receiver operating characteristic of the PCPE-1 level was 0.615 for the prediction of fibrosis (F0 vs. F1-6) (P=0.039). CONCLUSION: Serum PCPE-1 might be used as a noninvasive marker of liver fibrosis. Further animal and human studies are needed to assess the utility of this marker.

The effect of thyroid autoimmunity on T-cell responses in early pregnancy.

Thyroid autoimmunity (TAI) is common in women of reproductive age. There is a relationship between TAI and recurrent pregnancy loss and infertility. In pregnant patients with thyroid autoimmunity, the T helper-1 (Th1)/T helper-2 (Th2) ratio may shift to a Th1-type response and these activated T lymphocytes may lead to implantation failure. The aims of this study were to investigate the serum levels of Th1-, Th2-, and T-helper-17-(Th17)-associated cytokines in pregnant patients with TAI, and to evaluate how these cytokines change with l-thyroxin treatment during pregnancy. Twenty pregnant women with TAI diagnosed in the first trimester of pregnancy who were not on l-thyroxine treatment, 14 pregnant women with known TAI before pregnancy already been on l-thyroxine treatment, and 19 pregnant patients without TAI were included in this study. Thyroid function tests, thyroid autoantibodies, and cytokine levels were measured at the first and the second trimesters. In pregnant patients who were diagnosed with TAI in the first trimester, both serum IL-2 levels and IL-17 levels were significantly higher than those of the control group. There were no significant differences between groups for serum IL-4, IL-6, IL-23, IL-10, and IFNγ levels. In the second trimester, no significant differences were found between groups for all the cytokines measured. There are significant differences in Th1- and Th17-associated cytokine levels between patients with TAI and the control group in the first trimester. In the second trimester cytokine levels were similar among all groups. This pattern may be associated with the clinical benefits of l-thyroxine treatment.