Acute paretic syndrome in juvenile White Leghorn chickens resembles late stages of acute inflammatory demyelinating polyneuropathies in humans

Abstract

BackgroundSudden limb paresis is a common problem in White Leghorn flocks, affecting about 1% of the chicken population before achievement of sexual maturity. Previously, a similar clinical syndrome has been reported as being caused by inflammatory demyelination of peripheral nerve fibres. Here, we investigated in detail the immunopathology of this paretic syndrome and its possible resemblance to human neuropathies.MethodsNeurologically affected chickens and control animals from one single flock underwent clinical and neuropathological examination. Peripheral nervous system (PNS) alterations were characterised using standard morphological techniques, including nerve fibre teasing and transmission electron microscopy. Infiltrating cells were phenotyped immunohistologically and quantified by flow cytometry. The cytokine expression pattern was assessed by quantitative real-time PCR (qRT-PCR). These investigations were accomplished by MHC genotyping and a PCR screen for Marek's disease virus (MDV).ResultsSpontaneous paresis of White Leghorns is caused by cell-mediated, inflammatory demyelination affecting multiple cranial and spinal nerves and nerve roots with a proximodistal tapering. Clinical manifestation coincides with the employment of humoral immune mechanisms, enrolling plasma cell recruitment, deposition of myelin-bound IgG and antibody-dependent macrophageal myelin-stripping. Disease development was significantly linked to a 539 bp microsatellite in MHC locus LEI0258. An aetiological role for MDV was excluded.ConclusionsThe paretic phase of avian inflammatory demyelinating polyradiculoneuritis immunobiologically resembles the late-acute disease stages of human acute inflammatory demyelinating polyneuropathy, and is characterised by a Th1-to-Th2 shift.

Immunopathology and Th1/Th2 immune response of Campylobacter jejuni-induced paralysis resembling Guillain–Barré syndrome in chicken

“…Nobody has shown conclusive evidence that autoreactive T-cell response is observed in patients with GBS, indicating that EAN is not a true model of AIDP [26]. Like AIDP and EAN, inflammatory demyelinating polyradiculoneuropathy in avian is characterized by infiltration of nerve roots and peripheral nerves with macrophages and lymphocytes and, most importantly, a cell-mediated demyelination [23,24] that supports our present findings. A bird from 15th and 20th PID had no lymphocytic infiltration but prominently axonal degeneration with some paranodal demyelination.…”

“…The birds who developed GBS-like symptoms presented with variable pathological findings. Recently, Bader et al [23] reported the paretic phase of avian inflammatory demyelinating polyradiculoneuritis resembles the late-acute phase of human AIDP and is characterized by severe demyelination of peripheral nerves associated with multifocal endoneurial infiltration of lymphocytes and macrophages [23]. In the present study, teased nerve fiber preparations in experimental chickens showed the severe degenerative changes that included perinodal and/or patchy demyelination, Wallerian-like degeneration at the peak of the disease; whereas incomplete remyelination of the fibers was observed during the recovery phase.…”

“…It is well known that all C. jejuni infected individuals do not develop GBS; some individuals remain asymptomatic and may have sub-clinical/asymptomatic C. jejuni infection that can also lead to GBS [21]. Chicken used as an animal model in some studies showed that they develop both axonal (AMAN) and demyelinating (AIDP) subtypes of the disease [19,23]. Our infected birds had some differences in their disease course as compared to Li et al [19] who reported that all 33 (100%) birds fed with C. jejuni isolated from a patient with AMAN developed diarrhea and 18 (55%) of them had subsequent neurological illness.…”

“…The pathology of these birds resembles with the AIDP pattern in which relative prominence of demyelination corresponds roughly with the relative abundance of lymphocytic infiltration [14]; axonal degeneration is a bystander effect to this intense inflammation. To date, EAN is the most frequently used animal model for the investigation of immunological mechanism in acute inflammatory demyelinating disease of the PNS [23,24]. Though it resembles AIDP histopathologically, there are several disadvantages and dissimilarities to the human disease [25].…”

Evaluation of lumbosacral nerve root conduction in chickens by electrophysiological testing including high-resolution spinal magnetic stimulation

“…The value of juvenile chickens in neurological research recently has been emphasized by the highly prevalent GBSlike avian inflammatory demyelinating polyradiculoneuropathy (AvIDP) (Bader et al, 2010) as well as in previous work on inflammatory polyneuropathies (Bacon et al, 2001). These potentially overlapping syndromes and the classical form of Marek's disease Stevens et al, 1981) provide naturally occurring alternatives to experimental animal models for human inflammatory demyelinating polyradiculoneuropathies (IDPs).…”