Neuromyelitis optica (NMO) is an autoimmune, demyelinating disorder of the central nervous system (CNS) with typical clinical manifestations of optic neuritis and acute transverse myelitis attacks. Previously believed to be a variant of multiple sclerosis (MS), it is now considered an independent disorder which needs to be differentiated from MS. The discovery of autoantibodies against aquaporin-4 (AQP4-IgGs) changed our understanding of NMO immunopathogenesis and revolutionized the diagnostic process. AQP4-IgG is currently regarded as a specific biomarker of NMO and NMO spectrum disorders (NMOsd) and a key factor in its pathogenesis. Nevertheless, AQP4-IgG seronegativity in 10%–25% of NMO patients suggests that there are several other factors involved in NMO immunopathogenesis, i.e., autoantibodies against aquaporin-1 (AQP1-Abs) and antibodies against myelin oligodendrocyte glycoprotein (MOG-IgGs). This manuscript reviews current knowledge about NMO immunopathogenesis, pointing out the controversial issues and showing potential directions for future research. Further efforts should be made to broaden our knowledge of NMO immunology which could have important implications for clinical practice, including the use of potential novel biomarkers to facilitate an early and accurate diagnosis, and modern treatment strategies improving long-term outcome of NMO patients.

Small Heat shock proteins (sHsp) are a group of chaperone proteins. Under conditions of stress, the expression of sHsp is increased. Therefore, they are implicated in the pathogenesis of various autoimmune-mediated disorders and cancer. The purpose of this study was to analyze sHsp expression in exosomes from patients with gynecologic cancers and correlate these results with markers of cytotoxic immune response. The study group included patients with ovarian cancer, endometrial cancer, and patients with endometriosis. The levels of sHsps and cytotoxic markers were analyzed in serum, peritoneal fluid and exosomes using ELISA method. We found the highest levels of sHsp in exosomes from patients with ovarian cancer, but they were also elevated in patients with endometrial cancer and endometriosis. Moreover, we identified the presence of small Hsps in serum and peritoneal fluid in all study groups, but again the highest level was in patients with ovarian cancer. Small Hsps expression levels were positively correlated with markers of cytotoxic immune response.

Objective:To compare clinical characteristics across immunopathological subtypes of patients with multiple sclerosis.Methods:Immunopathological subtyping was performed on specimens from 547 patients with biopsy and/or autopsy confirmed CNS demyelination.Results:The frequency of immunopathological subtypes were pattern I (23%), II (56%), and III (22%). Immunopatterns were similar in terms of age at autopsy/biopsy (median age 41 years, range 4-83 years, p=0.16) and proportion female (54%, p=0.71). Median follow-up after symptom onset was 2.3 years (range 0-38y). In addition to being overrepresented among autopsy cases (45% vs. 19% in biopsy cohort, p<0.001), index attack-related disability was higher in pattern III vs. pattern II (median EDSS 4 vs. 3, p=0.02). Monophasic clinical course was more common in patients with pattern III than pattern I or II (59% vs. 33% vs. 32%, p<0.001). Similarly, patients with pattern III pathology were likely to have progressive disease compared to patients with patterns I or II, when followed for ≥5 years (24% overall, p=0.49), with no differences in long-term survival, despite a more fulminant attack presentation.Conclusion:All three immunopatterns can be detected in active lesions, although they are found less frequently later into the disease due to the lower number of active lesions. Pattern III is associated with a more fulminant initial attack than either pattern I or II. Biopsied patients appear to have similar long-term outcomes irrespective of their immunopatterns. Progressive disease is less associated with the initial immunopattern and suggests convergence into a final common pathway related to the chronically denuded axon.

213 www.journals.viamedica.pl/neurologia_neurochirurgia_polska Agata Czarnowska et al., SARS-CoV-2 infection in MS patients treated with disease-modifying therapies

Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS) with unknown etiology. It was recently suggested that autoimmunity, which had long been considered to be destructive in MS, might also play a protective role in the CNS of MS patients. Neurotrophins are polypeptides belonging to the neurotrophic factor family. While neurotrophins mediate cell survival and proliferation in the nervous system, they are also expressed within peripheral blood mononuclear cells fraction (PBMCs) of immunological system. In MS additional neurotrophic support from PBMCs might compensate relative neurotrophins deficiency in the damaged CNS tissue that needs to be repaired. Failure to produce the adequate neurotrophins concentrations might result in decreased protection of the CNS, consequently leading to increased atrophy, which is the main determinant of MS patients’ end-point disability. There are several lines of evidence, both from clinical research and animal models, suggesting that neurotrophins play a pivotal role in neuroprotective and neuroregenerative processes that are often defective in the course of MS. It seems that neuroprotective strategies might be used as potentially valuable add-on therapies, alongside traditional immunomodulatory treatment in multiple sclerosis.

No abstract

Vaccines work by stimulating the immune system, and their immunogenicity is key in achieving protection against specific pathogens. Questions have been raised whether in Multiple Sclerosis (MS) patients they could induce disease exacerbation and whether vaccines could possibly act as a trigger in the onset of MS in susceptible populations. So far, no correlation has been found between the vaccinations against influenza, hepatitis B, tetanus, human papillomavirus, measles, mumps, rubella, varicella zoster, tuberculosis, yellow fever, or typhoid fever and the risk of MS. Further research is needed for the potential protective implications of the tetanus and Bacillus Calmette–Guerin vaccines in MS patients. Nowadays with the emerging coronavirus disease 2019 (COVID-19) and recent vaccinations approval and arrival, the risk-benefit in MS patients with regards to safety and efficacy of COVID-19 vaccination in those treated with immunosuppressive therapies is of paramount importance. In this manuscript, we demonstrate how different vaccine types could be related to the immunopathogenesis of MS and discuss the risks and benefits of different vaccinations in MS patients.

No abstract