Epitope analyses of AT AA and

Epitope analyses of AT1-AA and ET-AA indicate that the IRAK inhibitor 1 receptor of both autoantibodies are located at the second extracelluar loop of both receptors. The specific epitopes for both autoantibodies are similar to what was reported previously in a cohort of patients from Brazil [6] and for AT1-AA also from North America [20], and European patients [5]. In the bioassay the endothelin receptor autoantibodies induce a negative chronotropic effect on cardiomyocytes which is different from the effect of the Angiotensin II receptor I autoantibodies. However, the effect on the in-vitro cultures of cardiomyocytes from newborn rats may differ f'rom the physiological effect of stimulation of the endothelin receptor on vascular smooth muscle cells. Therefore the pathophysiological effects of ETA-AA in preeclampsia are awaiting further studies. Plasma IL-17A [21], [22], [23] and Il-17 producing CD3 + CD4 + T lymphocytes [24] are reported to be increased in patients with preeclampsia. Plasma IL-17 is also increased in RUPP rats and in normal pregnant rats supplemented with CD + T cells from RUPP rats [25]. Our results show that a subgroup of patients with severe preeclampsia or HELLP syndrome express high concentrations of IL-17A, and that the same patients express high levels in blood samples from the first trimester (gestational week 8–10). Although a high concentration of IL17 was almost exclusively seen in the group of patients which developed severe preeclampsia or HELLP syndrome, a large group of patients with severe PE/HELLP expressed IL-17A below the detection limit of the assay. We did not find any significant difference in clinical or biochemical biomarkers between the two groups. Detection of IL-17A early in blood samples from gestational week 5–16 was also investigated by Salazar et al. [25], who reported that patients who later developed preeclampsia had a significantly higher percentage of CD4 + IL-17 + out of total CD4 + T cells, as compared to patients who did not develop preeclampsia. Together these results suggest that a subgroup of pregnant women displayed a proinflammatory state with an increased concentration of Th17 cells and increased Plasma IL-17A already in the first trimester, and that this is associated with the risk of developing pregnancy-induced hypertensive disorders.
Competing interests
Funding The study was supported by a grant from the Independent Research Fund Denmark, and Bagermester August Jensen og Hustrus legat.
Introduction Spinal cord injury (SCI) is a devastating condition affecting about 2.5 million people worldwide which compromises major motor, sensory, autonomic and reflex functions and profoundly impacts on the quality of life, life expectancy and health expenses [1]. The neurologic damage caused by SCI is the result of two distinct events, a primary and a secondary injury, which involve different mechanisms [2], [3]. Primary injury refers strictly to the cell death directly resultant from traumatic mechanical damage, which usually affects spinal grey matter to a greater extent than white matter. Secondary injury starts with the onset of inflammation and is characterized by increased blood-brain barrier permeability, glial and neuronal cell apoptosis, alongside a complex neuroinflammatory response that may last for months and years after the initial trauma [2], [4]. Patients with SCI often develop chronic neuropathic pain, which further deteriorates their quality of life [5]. This condition results from functional and structural plastic changes that occur centrally following injury to spinal cord neurons and glia, and include changes in receptor function and signaling mechanisms leading to increased neuronal excitability in somatosensory pathways [6]. Currently, the treatment options available for neuropathic pain following SCI are limited, only modestly effective and have serious side effects that frequently limit their usefulness [7], [8], [9]. Thus, considerable efforts have been directed at identifying novel targets of drug action which could lead to improved treatment of SCI-induced neuropathic pain.