Whole spinal transverse myelitis in neuromyelitis optica spectrum disorder.

BACKGROUND: Spinal cord is one of the prominent targets of autoimmune mechanisms in Neuromyelitis Optica Spectrum Disorder (NMOSD). Rarely, NMOSD causes damage to the entire length of the spinal cord, from cervical segments to conus medullaris, which has not been characterized in the existing literature. MATERIAL AND METHOD: We reviewed medical records, demographic information, and magnetic resonance imaging (MRI) sequences of 174 NMOSD patients from January 2011 to January 2023 who were admitted to Isfahan Multiple Sclerosis center to find patients with whole spinal transverse myelitis (TM). RESULTS: Whole spinal TM was present in five patients (2.9 %). Three patients were seropositive for Aquaporin-4 (AQP4) antibody; Myelin Oligodendrocyte Glycoprotein antibody (MOG IgG) tested negative for all of them. Lower limb weakness was the most frequent clinical complaint. Two patients presented with optic neuritis; One patient reported having episodes of nausea and vomiting. These patients, overall, yielded a higher expanded disability status scale (EDSS) score than the other NMOSD patients. CONCLUSION: Whole spinal TM is a rare finding in NMOSD, which is strongly associated with a higher severity and a worse outcome of the disease. The role of anti-AQP4 antibodies in the extent of myelitis in NMOSD has yet to be investigated.

Simulation and Stability Assessment of Anti-EpCAM Immunotoxin for Cancer Therapy.

Purpose: Epithelial cell adhesion molecule (EpCAM) is a dominant antigen in human colon carcinoma tissue. Topology features of this antigen are different in normal and malignant conditions; for instance, EpCAM is much less accessible to antibodies in normal cells than in cancerous tissues. Hence, EpCAM has been considered as a suitable candidate for cancer target therapy via immunotoxins (ITs) development. In this study, attention was focused on the stability assessment of anti-EpCAM-IT (anti-Ep-IT) to design a novel IT. Methods: The 3D structures of the antibody template and the toxin segment of anti-Ep-IT were retrieved from PDB. Discovery Studio3.0 was used to separate the ligands and water molecules. The antibody (Ab) fragment of anti-Ep-IT was aligned using protein blast (BLAST-p), and SWISS-MODEL database was used for Ab modeling. IT modeling was accomplished using MODELLER 9.15. Also, GROMACS 5.07 was used for molecular dynamic (MD) simulation step. Moreover, ERRAT and RAMPAGE databases were used for quality assessment of the structures. Results: BLAST-p results indicated that antibody moiety of IT has the highest E-value and query coverage scores to the monoclonal antibody (mAb) 4D5MOC-B. Modeling by SWISS-MODEL provided a reasonable template for Ab portion compared to MODELLER. The best modeled full-length IT with the lowest RMSD values was selected. Finally, RMSD plot for MD stage demonstrated constant values from 7000ps to 20000ps. Conclusion: In general, both modeling results and their quality evaluations were satisfactory for designing IT. Moreover, RMSD plot revealed that IT stability was preserved during the simulation. Overall, our findings led to modeling and simulation of the anti-Ep-IT with more structural stability.