Plasma cells (PC) are found in the CNS of multiple sclerosis (MS) patients, yet their source and role in MS remains unclear. We find that some PC in the CNS of mice with experimental autoimmune encephalomyelitis (EAE) originate in the gut and produce immunoglobulin A (IgA). Moreover, we show that IgA + PC are dramatically reduced in the gut during EAE, and likewise, a reduction in IgA-bound fecal bacteria is seen in MS patients during disease relapse. Removal of plasmablast (PB) plus PC resulted in exacerbated EAE that was normalized by the introduction of gut-derived IgA + PC. Furthermore, mice with an over-abundance of IgA + PB and/or PC were specifically resistant to the effector stage of EAE, and expression of interleukin (IL)-10 by PB plus PC was necessary and sufficient to confer resistance. Our data show that IgA + PB and/or PC mobilized from the gut play an unexpected role in suppressing neuroinflammation.
Conflict of interest: JLG held a sponsored research agreement with Novartis that funded this work and currently holds funding from EMD Serono. VR received a consulting honorarium from EMD Serono and Fluidigm. BNH is an employee of Novartis.
Replantation is the process of reattaching amputated parts. Relative indications for replantation in the upper extremity include amputation of the thumb or multiple digits as well as amputations proximal to zone II and pediatric finger amputations at any level. Preoperatively, the part should be sealed in a bag and placed on ice; maximum ischemia times are approximately 12 hours of warm and 24 hours of cold time for digits, with shorter times tolerated for amputations at more proximal levels. With multiple digit involvement, an assembly line approach is used in the operating room. Postoperatively, close attention must be paid to detect thrombosis because secondary ischemia times are shorter. Success rates vary; survival is predicted in part by the mechanism of injury, with sharp cut injuries having better outcomes. There is no consensus on appropriate postoperative anticoagulation, the number of vessels that must be anastomosed, or whether replantations should be centralized or performed in every hospital.
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