RESUMEN
We describe the case of an 82-year-old female referred to the vascular clinic for further evaluation and management of suspected inferior vena cava (IVC) thrombosis. She had previously presented to the general practitioner with a one-week history of vague abdominal pain in the right and left loins. Contrast-enhanced magnetic resonance imaging (MRI) of the abdomen and magnetic resonance angiography/magnetic resonance venography (MRA/MRV) revealed a 10 cm filling defect in the IVC, with the inferior margin of ≈5.8 cm proximal to the aortic bifurcation and its superior margin in the intrahepatic portion of the IVC. The filling defect had a transverse diameter of 2.6 cm and displayed heterogenous enhancement with contrast. We performed an endovascular biopsy with fluoroscopy (anteroposterior {AP} and lateral views) being utilized throughout the procedure to locate the mass and position the forceps in the tumor bed. The IVC was accessed via the right common femoral vein with a 10F catheter sheath. The sheath was advanced using the Seldinger technique to within ≈1 cm of the mass; then, a biopsy forceps (Micro-Tech single-use 8.5 mm biopsy forceps, Nanjing, China) was inserted, and six tissue samples were obtained. We report this case to add to the growing evidence that endovascular biopsy of IVC tumors can be performed safely and effectively.
RESUMEN
Background: Although myelin is composed of mostly lipids, the pathological role of myelin lipids in demyelinating diseases remains elusive. The principal lipid of the myelin sheath is ß-galactosylceramide (ß-Galcer). Its α-anomer (α-Galcer) has been demonstrated to be antigenically presented by macrophages via CD1d, a MHC class I-like molecule. Myelin, which is mostly composed of ß-Galcer, has been long considered as an immunologically-inert neuron insulator, because the antigen-binding cleft of CD1d is highly α-form-restricted. Results: Here, we report that CD1d-mediated antigenic presentation of myelin-derived galactosylceramide (Mye-GalCer) by macrophages contributed significantly to the progression of experimental autoimmune encephalomyelitis (EAE). Surprisingly, this presentation was recognizable by α-Galcer:CD1d-specific antibody (clone L363), but incapable of triggering expansion of iNKT cells and production of iNKT signature cytokines (IFNγ and IL-4). Likewise, a synthesized analog of Mye-Galcer, fluorinated α-C-GalCer (AA2), while being efficiently presented via CD1d on macrophages, failed to stimulate production of IFNγ and IL-4. However, AA2 significantly exacerbated EAE progression. Further analyses revealed that the antigenic presentations of both Mye-GalCer and its analog (AA2) in α-form via CD1d promoted IL-17 production from T cells, leading to elevated levels of IL-17 in EAE spinal cords and sera. The IL-17 neutralizing antibody significantly reduced the severity of EAE symptoms in AA2-treated mice. Furthermore, D-sphingosine, a lipid possessing the same hydrophobic base as ceramide but without a carbohydrate residue, efficiently blocked this glycolipid antigen presentation both in vitro and in spinal cords of EAE mice, and significantly decreased IL-17 and ameliorated the pathological symptoms. Conclusion: Our findings reveal a novel pathway from the presentation of Mye-GalCer to IL-17 production, and highlight the promising therapeutic potential of D-sphingosine for the human disorder of multiple sclerosis.