Inflammatory neuropathies: pathology, molecular markers and targets for specific therapeutic intervention

Abstract

Inflammatory neuropathies encompass groups of heterogeneous disorders characterized by pathogenic immune-mediated hematogenous leukocyte infiltration of peripheral nerves, nerve roots or both, with resultant demyelination or axonal degeneration or both. Inflammatory neuropathies may be divided into three major disease categories: Guillain-Barré syndrome (particularly the acute inflammatory demyelinating polyradiculoneuropathy variant), Chronic inflammatory demyelinating polyradiculoneuropathy and nonsystemic vasculitic neuropathy (or peripheral nerve vasculitis). Despite major advances in molecular biology, pathology and genetics, the pathogenesis of these disorders remains elusive. There is insufficient knowledge on the mechanisms of hematogenous leukocyte trafficking into the peripheral nervous system to guide the development of specific molecular therapies for immune-mediated inflammatory neuropathies compared to disorders such as psoriasis, inflammatory bowel disease, rheumatoid arthritis or multiple sclerosis. The recent isolation and characterization of human endoneurial endothelial cells that form the blood-nerve barrier provides an opportunity to elucidate leukocyte-endothelial cell interactions critical to the pathogenesis of inflammatory neuropathies at the interface between the systemic circulation and peripheral nerve endoneurium. This review discusses our current knowledge of the classic pathological features of inflammatory neuropathies, attempts at molecular classification and genetic determinants, the utilization of in vitro and in vivo animal models to determine pathogenic mechanisms at the interface between the systemic circulation and the peripheral nervous system relevant to these disorders and prospects for future potential molecular pathology biomarkers and targets for specific therapeutic intervention.

Периферійна Нейропатія При Хламідійному Реактивному Артриті

“…. Под-черкнем, что в патогенезе синдрома Гийена -Барре при болезнях суставов участвуют микрососудистые расстройства с эндотелиальной дисфункцией сосудов [15], гиперпродукция провоспалительных цитокинов [15], появление в крови антигликосфинголипидных антител [1,3,13].…”

“…взрослого населения [15]. У больных с другими артритами (ревматоидный, псориатиче-ский, анкилозирующий спондилит) уже достаточно хорошо известно развитие ПНП [6,9,12], тогда как при РХА такое поражение нервной системы пока описывается в виде единичных наблюдений, хотя нейропатия считается прогнознегативным фактором течения этого заболевания [14].…”

Gap Junction Coupled Cells, Barriers and Systemic Inflammation

“…Leukocyte-endothelial cell interactions are observed in the BNB during different inflammatory diseases [7].…”

“…In several diseases it is leukocyte trafficking into the peripheral nervous system, with an influence on leukocyteendothelial cells leading to disruption in the BNB that lead to inflammatory neuropathies, seen in Guillain-Barré syndrome, chronic inflammatory demyelinating polyradiculoneuropathy, and vasculitic neuropathies [4,7]. In OA it is a loss of osteochondral integrity that removes the barrier between intraarticular and subchondral compartments, and an invasion by blood vessels and sensory nerves occur [3].…”

“…Many human diseases, stroke, infectious and inflammatory processes, Alzheimer's disease, Parkinson's disease, HIV, obesity, type 2 diabetes, atherosclerosis, allergy, age-related macular degeneration (AMD), glaucoma, osteoarthritis (OA), systemic vasculitis, and cardiovascular diseases seem to have features in common, where there is a disruption of homeostasis, and they are nearly universally associated with systemic chronic inflammation [1][2][3][4][5][6][7][8]. Inducers of inflammation trigger the production of inflammatory mediators, which in turn alter the functionality of tissues and organs.…”