scholarly journals Autoantibody screening in Guillain-Barre Syndrome

Author(s):  
Cinta Lleixà ◽  
Lorena Martín-Aguilar ◽  
Elba Pascual-Goñi ◽  
Teresa Franco ◽  
Marta Caballero ◽  
...  

Guillain-Barre Syndrome (GBS) is an acute inflammatory neuropathy with a heterogeneous presentation and pathogenesis. Serum antibodies against various gangliosides can be found in less than half of all patients in the acute phase of GBS but the target antigens remain unknown for the remaining half. Our work describes a comprehensive screening for serum autoantibodies targeting peripheral nerve tissue, cells, and purified antigens in a prospective GBS cohort including 100 patients. Our study confirms that (1) GBS patients display a very heterogeneous repertoire of autoantibodies targeting nerve cells and structures, (2) gangliosides are the most frequent antigens in GBS patients and have prognostic value, (3) a small subset of patients display antibodies targeting the myelin sheath, and (4) further antigen-discovery experiments are needed to elucidate other potential disease-specific autoantibodies in GBS.

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Cinta Lleixà ◽  
Lorena Martín-Aguilar ◽  
Elba Pascual-Goñi ◽  
Teresa Franco ◽  
Marta Caballero ◽  
...  

Abstract Background Guillain–Barré syndrome (GBS) is an acute inflammatory neuropathy with a heterogeneous presentation. Although some evidences support the role of autoantibodies in its pathogenesis, the target antigens remain unknown in a substantial proportion of GBS patients. The objective of this study is to screen for autoantibodies targeting peripheral nerve components in Guillain–Barré syndrome. Methods Autoantibody screening was performed in serum samples from all GBS patients included in the International GBS Outcome study by 11 different Spanish centres. The screening included testing for anti-ganglioside antibodies, anti-nodo/paranodal antibodies, immunocytochemistry on neuroblastoma-derived human motor neurons and murine dorsal root ganglia (DRG) neurons, and immunohistochemistry on monkey peripheral nerve sections. We analysed the staining patterns of patients and controls. The prognostic value of anti-ganglioside antibodies was also analysed. Results None of the GBS patients (n = 100) reacted against the nodo/paranodal proteins tested, and 61 (61%) were positive for, at least, one anti-ganglioside antibody. GBS sera reacted strongly against DRG neurons more frequently than controls both with IgG (6% vs 0%; p = 0.03) and IgM (11% vs 2.2%; p = 0.02) immunodetection. No differences were observed in the proportion of patients reacting against neuroblastoma-derived human motor neurons. Reactivity against monkey nerve tissue was frequently detected both in patients and controls, but specific patterns were only detected in GBS patients: IgG from 13 (13%) patients reacted strongly against Schwann cells. Finally, we confirmed that IgG anti-GM1 antibodies are associated with poorer outcomes independently of other known prognostic factors. Conclusion Our study confirms that (1) GBS patients display a heterogeneous repertoire of autoantibodies targeting nerve cells and structures; (2) gangliosides are the most frequent antigens in GBS patients and have a prognostic value; (3) further antigen-discovery experiments may elucidate other potential antigens in GBS.


2021 ◽  
Author(s):  
Alexander J Davies ◽  
Cinta Lleixà ◽  
Ana M Siles ◽  
Dawn Gourlay ◽  
Georgina Berridge ◽  
...  

Introduction Recent outbreaks of Zika virus (ZIKV) in South and Central America have highlighted significant neurological side effects. Concurrence with the inflammatory neuropathy Guillain-Barré syndrome (GBS) is observed in 1:4000 ZIKV cases. Whether the neurological symptoms of ZIKV infection are a consequence of autoimmunity or direct neurotoxicity is unclear. Methods We employed rat dorsal root ganglion (DRG) neurons, Schwann cells (SCs), and human stem cell-derived sensory neurons myelinated with rat SCs as cellular models to screen for anti-peripheral nerve reactive IgG and IgM autoantibodies in sera of ZIKV patients with and without GBS. In this study, 52 ZIKV-GBS patients were compared with 134 ZIKV-infected patients, and 91 non-ZIKV controls. Positive sera were taken forward for target identification by immunoprecipitation and mass spectrometry, and candidate antigens validated by ELISA and cell-based assays. Autoantibody reactions against glycolipid antigens were also screened on an array. Results Overall, IgG antibody reactivity to rat SCs (6.5%) and myelinated co-cultures (9.6%) were significantly higher, albeit infrequently, in the ZIKV-GBS group compared to all controls. IgM antibody immunoreactivity to DRGs (32.3%) and SCs (19.4%) was more frequently observed in the ZIKV-GBS group compared to other controls, while IgM reactivity to co-cultures was as common in ZIKV and non-ZIKV sera. Strong axonal-binding ZIKV-GBS serum IgG antibodies from one patient were confirmed to react with neurofascin-155 and 186. Serum from a ZIKV non-GBS patient displayed strong myelin-binding and anti-lipid antigen reaction characteristics. There was however no significant association of ZIKV-GBS with any anti-glycolipid antibodies. Conclusion Autoantibodies in ZIKV associated GBS patient sera target heterogeneous peripheral nerve antigens suggesting heterogeneity of the humoral immune response despite a common prodromal infection.


Author(s):  
V Karnik ◽  
T Roberts ◽  
W Johnston

Background: Standardized order sets are thought to improve patient outcomes in multiple ways. They reduce costs without reducing quality of care, and improve efficiency. In both surgical and medical conditions patients benefit from order sets in various disease states. In Guillain-Barre syndrome (GBS), the use of standardized order sets may be beneficial as there are a defined set of disease-specific diagnostic tests and treatments to be implemented. Here, the primary aim was to search for, and evaluate standardized order sets for GBS, and to provide a basis for development of future pathways. Methods: We used the Cochrane, TRIP, and MEDLINE/PUBMED databases, searching between January 1966 and April 2014. Search terms included: “Guillain-Barre Syndrome” and its synonyms, “(standardized) order set”, “clinical pathway”, “neurology” and “admission bundle.” Results: Despite anecdotal evidence of order sets, no formal data has been published showing benefit after implementation of these sets in GBS or any neurological condition. Conclusions: Although evidence exists for use of standardized order sets in surgical and medical settings, no published data exist in neurology. Given GBS has a defined set of disease-specific and state-specific treatment options, a standardized order set used on admission for GBS patients may prove to be beneficial.


2016 ◽  
Vol 127 (2) ◽  
pp. 1652-1656 ◽  
Author(s):  
Siti Nur Omaira Razali ◽  
Thaarani Arumugam ◽  
Nobuhiro Yuki ◽  
Faizatul Izza Rozalli ◽  
Khean-Jin Goh ◽  
...  

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