Guillain-Barré Syndrome-related campylobacter jejuni in Bangladesh: ganglioside mimicry and cross-reactive antibodies

BACKGROUND: <br/> Campylobacter jejuni is the predominant antecedent infection in Guillain-Barré syndrome (GBS). Molecular mimicry and cross-reactive immune responses to C. jejuni lipo-oligosaccharides (LOS) precipitate the development of GBS, although this mechanism has not been established in patients from developing countries. We determined the carbohydrate mimicry between C. jejuni LOS and gangliosides, and the cross-reactive antibody response in patients with GBS in Bangladesh.<br/> METHODOLOGY:<br/> Sera from 97 GBS patients, and 120 neurological and family controls were tested for antibody reactivity against LOS from C. jejuni isolates from GBS patients in Bangladesh (BD-07, BD-39, BD-10, BD-67 and BD-94) by enzyme-linked immunosorbent assay (ELISA). Cross-reactivity to LOS was determined by ELISA. The LOS outer core structures of C. jejuni strains associated with GBS/MFS were determined by mass spectrometry.<br/> PRINCIPLE FINDINGS:<br/> IgG antibodies to LOS from C. jejuni BD-07, BD-39, BD-10, and BD-67 IgG antibodies were found in serum from 56%, 58%, 14% and 15% of GBS patients respectively, as compared to very low frequency (<3%) in controls (p<0.001). Monoclonal antibodies specific for GM1 and GD1a reacted strongly with LOS from the C. jejuni strains (BD-07 and BD-39). Mass spectrometry analysis confirmed the presence of GM1 and GD1a carbohydrate mimics in the LOS from C. jejuni BD-07 and BD-39. Both BD-10 and BD-67 express the same LOS outer core, which appears to be a novel structure displaying GA2 and GD3 mimicry. Up to 90-100% of serum reactivity to gangliosides in two patients (DK-07 and DK-39) was inhibited by 50 µg/ml of LOS from the autologous C. jejuni isolates. However, patient DK-07 developed an anti-GD1a immune response while patient DK-39 developed an anti-GM1 immune response.<br/> CONCLUSION:<br/> Carbohydrate mimicry between C. jejuni LOS and gangliosides, and cross-reactive serum antibody precipitate the majority of GBS cases in Bangladesh

Neonatal Fc receptor promoter gene polymorphism does not predict pharmacokinetics of IVIg or the clinical course of GBS

Treatment of Guillain-Barré syndrome with a standard course of high-dose intravenous immunoglobulin (IVIg) results in a variable clinical recovery which is associated with changes in serum IgG levels after treatment. The neonatal Fc-receptor protects IgG from degradation, and a genetic polymorphism in its promoter region that influences the expression of Fc-receptor, may in part explain the variation in IgG levels and outcome. This polymorphism was determined by polymerase chain reaction in a cohort of 257 patients with Guillain-Barré syndrome treated with IVIg. We could not demonstrate a relation between this polymorphism, the pharmacokinetics of IVIg, or the clinical course and outcome

Can Campylobacter coli induce Guillain-Barré syndrome?

Campylobacter jejuni enteritis is the most frequently identified infection preceding the Guillain-Barr\ue9 syndrome (GBS) and neural damage is thought to be induced through molecular mimicry between C. jejuni lipo-oligosaccharide (LOS) and human gangliosides. It has been questioned whether or not other Campylobacter species, including C. curvus, C. upsaliensis and C. coli, could be similarly involved. This is relevant because it would imply that bacterial factors considered important in the aetiology of GBS crossed species barriers. Two prior reports have appeared where C. coli was putatively associated with a case of GBS.Peer reviewed: YesNRC publication: Ye

Genetic biomarkers for intravenous immunoglobulin response in chronic inflammatory demyelinating polyradiculoneuropathy

Background and purpose Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a clinical and electrophysiological heterogeneous immune-mediated polyneuropathy. Intravenous immunoglobulin (IVIg), corticosteroids, and plasma exchange are proven effective treatments for CIDP. The clinical response to IVIg is variable between patients and currently unexplained. Finding biomarkers related to treatment response can help to understand the diversity of CIDP and personalise treatment choice.Methods We investigated whether genetic variation between patients may explain some of these differences in treatment response. Based on previous publications, we selected six candidate genes that might affect immune and axonal functions, IVIg metabolism, and treatment response in CIDP. Genetic variants were assessed in 172 CIDP patients treated with at least one course of IVIg (2 g/kg). A response to IVIg was defined by >= 1 grade improvement on the modified Rankin Scale. Blood samples were tested for variations in CNTN2, PRF1, FCGRT, FCGR2B, GJB1, and SH2D2A genes.Results In univariate analysis, patients with the FCGR2B promoter variant 2B.4/2B.1 responded more often to IVIg than patients with the 2B.1/2B.1 variant (odds ratio [OR] = 6.9, 95% confidence interval [CI] = 1.6-30; p = 0.003). Patients with the p.(Ala91Val) variant of PRF1 were less often IVIg responsive (OR = 0.34, 95% CI = 0.13-0.91; p = 0.038). In multivariate analysis, both PRF1 and FCGR2B showed discriminative ability to predict the chance of IVIg response (area under the curve = 0.67).Conclusions Variations in PRF1 and the promoter region of FCGR2B are associated with the response to IVIg in CIDP. These findings, which require validation, are a first step towards the understanding of the heterogeneity in the treatment response in CIDP.Genetics of disease, diagnosis and treatmen

IVIg-induced plasmablasts in patients with Guillain-Barré syndrome

Objective: The Guillain–Barré syndrome (GBS) is an acute, immune-mediated disease of peripheral nerves. Plasmablasts and plasma cells play a central role in GBS by producing neurotoxic antibodies. The standard treatment for GBS is high-dose intravenous immunoglobulins (IVIg), however the working mechanism is unknown and the response to treatment is highly variable. We aimed to determine whether IVIg changes the frequency of B-cell subsets in patients with GBS. Methods: Peripheral blood mononuclear cells were isolated from 67 patients with GBS before and/or 1, 2, 4, and 12 weeks after treatment with high-dose IVIg. B-cell subset frequencies were determined by flow cytometry and related to serum immunoglobulin levels. Immunoglobulin transcripts before and after IVIg treatment were examined by next-generation sequencing. Antiglycolipid antibodies were determined by ELISA. Results: Patients treated with IVIg demonstrated a strong increase in plasmablasts, which peaked 1 week after treatment. Flow cytometry identified a relative increase in IgG2 plasmablasts posttreatment. Within IGG sequences, dominant clones were identified which were also IGG2 and had different immunoglobulin sequences compared to pretreatment samples. High plasmablast frequencies after treatment correlated with an increase in serum IgG and IgM, suggesting endogenous production. Patients with a high number of plasmablasts started to improve earlier (P = 0.015) and were treated with a higher dose of IVIg. Interpretation: High-dose IVIg treatment alters the distribution of B-cell subsets in the peripheral blood of GBS patients, suggesting de novo (oligo-)clonal B-cell activation. Very high numbers of plasmablasts after IVIg therapy may be a potential biomarker for fast clinical recovery

一般社団法人神緑会事業報告

Primary central nervous system phaeohyphomycosis is a fatal fungal infection due mainly to the neurotropic melanized fungi Cladophialophora bantiana , Rhinocladiella mackenziei , and Exophiala dermatitidis. Despite the combination of surgery with antifungal treatment, the prognosis continues to be poor, with mortality rates ranging from 50 to 70%. Therefore, a search for a more-appropriate therapeutic approach is urgently needed. Our in vitro studies showed that with the combination of amphotericin B and flucytosine against these species, the median fractional inhibitory concentration (FIC) indices for strains ranged from 0.25 to 0.38, indicating synergy. By use of Bliss independence analysis, a significant degree of synergy was confirmed for all strains, with the sum ΔE ranging from 90.2 to 698.61%. No antagonism was observed. These results indicate that amphotericin B, in combination with flucytosine, may have a role in the treatment of primary cerebral infections caused by melanized fungi belonging to the order Chaetothyriales . Further in vivo studies and clinical investigations to elucidate and confirm these observations are warranted

Genetic biomarkers for intravenous immunoglobulin response in chronic inflammatory demyelinating polyradiculoneuropathy

Background and purpose: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a clinical and electrophysiological heterogeneous immune-mediated polyneuropathy. In

An Inside Look at Sunspot Oscillations with Higher Azimuthal Wavenumbers

Solar chromospheric observations of sunspot umbrae offer an exceptional view of magneto-hydrodynamic wave phenomena. In recent years, a wealth of wave signatures related to propagating magneto-acoustic modes have been presented, which demonstrate complex spatial and temporal structuring of the wave components. Theoretical modelling has demonstrated how these ubiquitous waves are consistent with an m=0 slow magneto-acoustic mode, which are excited by trapped sub-photospheric acoustic (p-mode) waves. However, the spectrum of umbral waves is broad, suggesting that the observed signatures represent the superposition of numerous frequencies and/or modes. We apply Fourier filtering, in both spatial and temporal domains, to extract chromospheric umbral wave characteristics consistent with an m=1 slow magneto-acoustic mode. This identification has not been described before. Angular frequencies of 0.037 +/- 0.007 rad/s (2.1 +/- 0.4 deg/s), corresponding to a period approximately 170 s for the m=1 mode are uncovered for spatial wavenumbers in the range of 0.45<k<0.90 arcsec^-1 (5000-9000 km). Theoretical dispersion relations are solved, with corresponding eigenfunctions computed, which allows the density perturbations to be investigated and compared with our observations. Such magnetohydrodynamic modelling confirms our interpretation that the identified wave signatures are the first direct observations of an m=1 slow magneto-acoustic mode in the chromospheric umbra of a sunspot

Neutron spectroscopy of 26Mg states : Constraining the stellar neutron source 22Ne(α,n)25Mg

This work reports on accurate, high-resolution measurements of the 25Mg(n,γ)26Mg and 25Mg(n,tot) cross sections in the neutron energy range from thermal to about 300 keV, leading to a significantly improved 25Mg(n,γ)26Mg parametrization. The relevant resonances for n+25Mg were characterized from a combined R-matrix analysis of the experimental data. This resulted in an unambiguous spin/parity assignment of the corresponding excited states in 26Mg. With this information experimental upper limits of the reaction rates for 22Ne(α,n)25Mg and 22Ne(α,γ)26Mg were established, potentially leading to a significantly higher (α,n)/(α,γ) ratio than previously evaluated. The impact of these results has been studied for stellar models in the mass range 2 to 25 M⊙