Taken together, these data demonstrate that exogenous IL-4 and IL-10 administration concurrently during pregnancy can normalize immune cell subsets and prevent PE induced by maternal immune system activation.
Excessive innate immune system activation and inflammation during pregnancy can lead to organ injury and dysfunction and preeclampsia (PE); however, the molecular mechanisms involved are unknown. We tested the hypothesis that Toll-like receptor (TLR) activation induces major histocompatibility complex (MHC) class II invariant chain peptide (CLIP) expression on immune cells, makes them pro-inflammatory, and are necessary to cause PE-like features in mice. Treatment with VG1177, a competitive antagonist peptide for CLIP in the groove of MHC class II, was able to both prevent and treat PE-like features in mice. We then determined that γ-δ T cells are critical for the development of PE-like features in mice since γ-δ T-cell knockout mice, like CLIP deficient mice, are resistant to developing PE-like features. Placentas from women with PE exhibit significantly increased levels of γ-δ T cells. These preclinical data demonstrate that CLIP expression and activated γ-δ T cells are responsible for the development of immunologic PE-like features and that temporarily antagonizing CLIP and/or γ-δ T cells may be a therapeutic strategy for PE.
Only a very few cases of subarachnoid hemorrhage due to isolated anterior spinal artery aneurysms have been reported in the literature. We report a case of subarachnoid hemorrhage due to anterior spinal artery aneurysm rupture in a renal transplant patient at our institution. A 47-year-old male had abrupt onset of left lower extremity weakness with bowel and bladder disturbances which prompted emergent surgical evacuation of the clot and hence immediate diagnostic angiography was not performed. However, follow-up serial intracranial arterial ultrasound studies showed only vasospasm of the basilar artery. Repeat MRI of the thoracic spine showed persistence of subarachnoid blood products, but no larger foci compared to previous imaging. When spinal subarachnoid hemorrhage is present in the appropriate clinical setting, isolated anterior spinal artery aneurysm should be considered as a possible, treatable cause.
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