Differential binding patterns of anti-sulfatide antibodies to glial membranes

Sulfatide is a major glycosphingolipid in myelin and a target for autoantibodies in autoimmune neuropathies. However neuropathy disease models have not been widely established, in part because currently available monoclonal antibodies to sulfatide may not represent the diversity of anti-sulfatide antibody binding patterns found in neuropathy patients. We sought to address this issue by generating and characterising a panel of new anti-sulfatide monoclonal antibodies. These antibodies have sulfatide reactivity distinct from existing antibodies in assays and in binding to peripheral nerve tissues and can be used to provide insights into the pathophysiological roles of anti-sulfatide antibodies in demyelinating neuropathies

Guillain-Barré Syndrome Outbreak in Peru 2019 Associated With Campylobacter jejuni Infection

OBJECTIVE: To identify the clinical phenotypes and infectious triggers in the 2019 Peruvian Guillain-Barré syndrome (GBS) outbreak. METHODS: We prospectively collected clinical and neurophysiologic data of patients with GBS admitted to a tertiary hospital in Lima, Peru, between May and August 2019. Molecular, immunologic, and microbiological methods were used to identify causative infectious agents. Sera from 41 controls were compared with cases for antibodies to Campylobacter jejuni and gangliosides. Genomic analysis was performed on 4 C jejuni isolates. RESULTS: The 49 included patients had a median age of 44 years (interquartile range [IQR] 30-54 years), and 28 (57%) were male. Thirty-two (65%) had symptoms of a preceding infection: 24 (49%) diarrhea and 13 (27%) upper respiratory tract infection. The median time between infectious to neurologic symptoms was 3 days (IQR 2-9 days). Eighty percent had a pure motor form of GBS, 21 (43%) had the axonal electrophysiologic subtype, and 18% the demyelinating subtype. Evidence of recent C jejuni infection was found in 28/43 (65%). No evidence of recent arbovirus infection was found. Twenty-three cases vs 11 controls (OR 3.3, confidence interval [CI] 95% 1.2-9.2, p < 0.01) had IgM and/or IgA antibodies against C jejuni. Anti-GM1:phosphatidylserine and/or anti-GT1a:GM1 heteromeric complex antibodies were strongly positive in cases (92.9% sensitivity and 68.3% specificity). Genomic analysis showed that the C jejuni strains were closely related and had the Asn51 polymorphism at cstII gene. CONCLUSIONS: Our study indicates that the 2019 Peruvian GBS outbreak was associated with C jejuni infection and that the C jejuni strains linked to GBS circulate widely in different parts of the world

Guillain-Barré syndrome following Zika virus infection is associated with a diverse spectrum of peripheral nerve reactive antibodies

Background and Objectives Recent outbreaks of Zika virus (ZIKV) in South and Central America have highlighted significant neurological side effects. Concurrence with the inflammatory neuropathy Guillain-Barr&#xE9; syndrome (GBS) is observed in 1:4000 ZIKV cases. Whether the neurological symptoms of ZIKV infection are immune-mediated is unclear. We employed rodent and human live cellular models to screen for anti-peripheral nerve reactive IgG and IgM autoantibodies in sera of ZIKV patients with and without GBS. Methods In this study, 52 ZIKV-GBS patients were compared with 134 ZIKV-infected patients without GBS, 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 reactivities to rat Schwann cells (SCs) (6.5%) and myelinated co-cultures (9.6%) were significantly higher, albeit infrequent, in the ZIKV-GBS group compared to all controls. IgM antibody immunoreactivity to dorsal root ganglia (DRG) neurones (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 putative anti-lipid antigen reaction characteristics. There was however no significant association of ZIKV-GBS with any known anti-glycolipid antibodies. Conclusion Autoantibody responses in ZIKV-GBS target heterogeneous peripheral nerve antigens suggesting heterogeneity of the humoral immune response despite a common prodromal infection

Guillain-Barre syndrome during the Zika virus outbreak in Northeast Brazil: An observational cohort study

Objective: To determine the clinical phenotype of Guillain-Barré syndrome (GBS) after Zika virus (ZIKV) infection, the anti-glycolipid antibody signature, and the role of other circulating arthropod-borne viruses, we describe a cohort of GBS patients identified during ZIKV and chikungunya virus (CHIKV) outbreaks in Northeast Brazil. Methods: We prospectively recruited GBS patients from a regional neurology center in Northeast Brazil between December 2014 and February 2017. Serum and CSF were tested for ZIKV, CHIKV, and dengue virus (DENV), by RT-PCR and antibodies, and serum was tested for GBS-associated antibodies to glycolipids. Results: Seventy-one patients were identified. Forty-eight (68%) had laboratory evidence of a recent arbovirus infection; 25 (52%) ZIKV, 8 (17%) CHIKV, 1 (2%) DENV, and 14 (29%) ZIKV and CHIKV. Most patients with a recent arbovirus infection had motor and sensory symptoms (72%), a demyelinating electrophysiological subtype (67%) and a facial palsy (58%). Patients with a recent infection with ZIKV and CHIKV had a longer hospital admission and more frequent mechanical ventilation compared to the other patients. No specific anti-glycolipid antibody signature was identified in association with arbovirus infection, although significant antibody titres to GM1, GalC, LM1, and GalNAc-GD1a were found infrequently. Conclusion: A large proportion of cases had laboratory evidence of a recent infection with ZIKV or CHIKV, and recent infection with both viruses was found in almost one third of patients. Most patients with a recent arbovirus infection had a sensorimotor, demyelinating GBS. We did not find a specific anti-glycolipid antibody signature in association with arbovirus-related GBS