Neurofascin (NF) 155-and NF186-Specific T Cell Response in a Patient Developing a Central Pontocerebellar Demyelination after 10 Years of CIDP

Background: Information and pathobiological understanding about central demyelinating manifestation in patients, who primarily suffer from chronic inflammatory demyelinating polyneuropathy (CIDP), are scarce. Methods: IFN-gamma-response as well as antibodies against the (para) nodal antigens neurofascin (NF) 155 and NF 186 had been tested by Elispot assay and ELISA before clinical manifestation and at follow-up. Case description and results: The patient described here developed a subacute brainstem syndrome more than 10 years after diagnosis of CIDP under low-dose maintenance treatment of intravenous immunoglobulins (IVIG). MRI revealed enhancing right-sided pontocerebellar lesion. CSF examination showed mild pleocytosis and elevated protein, and negative oligoclonal bands. Further diagnostics exclude differential diagnoses such as tuberculoma, sarcoidosis, or metastasis. Specific IFN-gamma response against NF155 and NF186 as measured by Elispot assay was elevated before clinical manifestation. NF155 and NF186 antibodies were negative. Escalation of IVIG treatment at 2 g/kg BW followed by 1.4 g/kg BW led to clinical remission albeit to a new asymptomatic central lesion. Follow-up NF155 and NF186-Elispot turned negative. Conclusion: The case reported here with a delayed central manifestation after an initially typical CIDP and NF155 and NF186 T cell responses does not resemble described cases of combined central and peripheral demyelination but may reflect a novel subtype within the great clinical heterogeneity of CIDP

Thermal behaviour of cermets and hardmetals during debinding and sintering

Most important processes during heat treatment of powder mixtures for production of cermets and hardmetals are drying, dewaxing, outgassing, melting of the binder phase and sintering. Results of sintering experiments on the lab scale are presented and discussed. The experiments include sintering of materials with various compositions of hard phases (WC, TiCN) and metallic binder phases (Co, Ni). The multiphase reactions are investigated by methods of thermal analysis (Thermodilatometry, Differential Thermal Analysis, Thermogravimetry). Selected microstructures are inspected by high resolution field emission scanning electron microscopy. The influence of furnace atmosphere (cermets in helium or nitrogen and hardmetals in helium) and gas pressure on gas reactions are investigated by a thermobalance-mass spectrometer-system. For these studies an orifice coupling system for normal pressure in the thermobalance (1000 mbar) was modified in order to use this system also at a pressure range of approximately 0.1 to 10 mbar. The achieved process knowledge enables better understanding for sintering cermets and hardmetals and to improve both the processes and the material quality

Optimization of the temperature program to scale up the stabilization of polyacrylonitrile fibers

The production of carbon fibers from polyacrylonitrile (PAN) includes a stabilization step before carbonization. Transferring this stabilization from the laboratory to a bigger scale cannot be performed without changes of the process parameters. Using a pure PAN polymer, fibers were spun and their stabilization as well as carbonization was studied in laboratory scale. The resulting materials were analyzed with FTIR, SEM and XRD. The stabilization step was then transferred to a pilot scale. Limitations given by the production line had to be taken into account to develop a suitable temperature treatment. The formation of a core/shell structure during stabilization was observed and was detrimental to the properties of the fiber after carbonization. Adjustments were made based on obtained results to balance the negative effects of high heating rates and strong temperature gradients. With the implemented changes the mechanical properties could be reproduced on the larger production scale

Neurofascin and Compact Myelin Antigen-Specific T Cell Response Pattern in Chronic Inflammatory Demyelinating Polyneuropathy Subtypes

ObjectiveThe objective of this study is to investigate whether chronic inflammatory demyelinating polyneuropathy (CIDP) and its subtypes differ in their type 1 T-helper (TH1) cell response against nodal/paranodal neurofascin (NF186, NF155) as well as myelin protein zero (P0 180–199) and myelin basic protein (MBP 82–100).MethodsInterferon-gamma (IFN-γ) enzyme-linked immunospot assay was used to detect antigen-specific T cell responses in 48 patients suffering typical CIDP (n = 18), distal acquired demyelinating polyneuropathy (n = 8), multifocal acquired demyelinating sensory and motor polyneuropathy (MADSAM; n = 9), and sensory CIDP (n = 13) compared to other non-immune polyneuropathy (ON; n = 19) and healthy controls (n = 9).ResultsCompared to controls, MADSAM and sensory CIDP patients showed broadest IFN-γ T cell responses to all four antigens. Positive IFN-γ responses against two or more antigens were highly predictive for CIDP (positive predictive value = 0.95) and were found in 77% of CIDP patients. Patients with limited antigen-specific response were females, more severely affected with neuropathic pain and proximal paresis. The area under the receiver operating characteristics curve (AUC) of NF186 in MADSAM was 0.94 [95% confidential interval (CI) 0.82–1.00] compared to ON. For sensory CIDP, AUC of P0 180–199 was 0.94 (95% CI 0.86–1.00) and for MBP 82–100 0.95 (95% CI 0.88–1.00) compared to ON.ConclusionCell-mediated immune responses to (para)nodal and myelin-derived antigens are common in CIDP. TH1 response against NF186 may be used as a biomarker for MADSAM and TH1 responses against P0 180–199 and MBP 82–100 as biomarkers for sensory CIDP. Larger multicenter studies study are warranted in order to establish these immunological markers as a diagnostic tools