Clinical and Experimental Neuroimmunology最新文献

The pathogenesis of neuronal damage in anti-Hu-antibody-positive paraneoplastic neurologic syndrome (Hu-PNS) is thought to be mediated by cytotoxic T lymphocyte (CTL). However, there is no direct evidence showing that antigen-specific T cells are the effector against neurons. Antigen-specific CTL-mediated cell death has been observed in cancer immunology, but not as a neurological disease model. The CTL-mediated etiology in PNS should be confirmed using in vivo model systems in the future. Herein, we present an ex vivo model of antigen-specific CTL against cultured neurons. A previous study showed the CTL activity of CD8⁺ T cells taken from the peripheral blood of patients with Hu-antibody-positive PNS against Hu-protein-derived-peptide-expressing autologous fibroblasts. Results revealed that the HuD peptide, which can bind to major histocompatibility complex (MHC) class I of Balb/c mice, stimulated CD8⁺ T cells collected from mice immunized with peptide-bound self-activated dendritic cells with murine CD40 ligand-transduced adenovirus vectors (AdmCD40L). Moreover, CTL activity against autologous neurons in culture was observed. Hence, this result could be used in the development of an in vivo model of CTL-induced neurological disorders, which can help in further understanding the pathogenesis of PNS.

Alemtuzumab is one of the most effective agents in the treatment of multiple sclerosis (MS). On the other hand, the spectrum of possible side effects is wide and carries the potential to cause a variety of inflammatory and thrombotic complications. In this report firstly, a case who developed a systemic thrombotic and inflammatory response after alemtuzumab administration and then presented with pretibial edema in a period of 1 month is discussed. Then, based on the findings detected via this case, the possible side effects of alemtuzumab, both during drug infusion and in the early and late periods after administration, were classified. This classification was created by compiling the reported adverse effects in the literature related to the use of alemtuzumab for the treatment of multiple sclerosis. This presented case shows that prothrombotic predisposition after alemtuzumab administration may result in peripheral microvascular circulatory disorders even in the long term and one of them is pretibial edema. According to the current literature data, side effects of alemtuzumab treatment which is used for multiple sclerosis are categorized as follows: (i) infusion-related reactions, (ii) acute/subacute inflammatory and pro-thrombotic effects, (iii) immunosuppression-related opportunistic infections, (iv) immune reconstitution-related secondary autoimmune disorders. Increasing awareness of the possible side effects of alemtuzumab treatment used in the course of multiple sclerosis will enable both the development of possible prophylactic treatment options and the early control of emerging complications.

We read with interest the comments made by Finsterer et al.¹ on our previously published case report “Guillain–Barré syndrome after coronavirus disease 2019 vaccine: A temporal association”.² We understand that the comments made are interesting points of discussion.

The main point questioned by Finsterer et al., the diagnosis of Guillain-Barré syndrome (GBS) as a temporal association, not necessarily causal, can be elucidated due to several components. First, due to the time the article was written, in which there were not as many cases reported in the literature as currently, as correctly described in the letter “In a recent review of the neurological side effects of SARS-CoV-2 vaccines, 300 cases of SC2VaG were described”.¹ Second, due to limited diagnostic resources in the case, a public hospital in southern Brazil. The absence of diagnostic tests, such as those mentioned by Finsterer et al. (electroneuromyography, investigation of cytokines, chemokines and glial markers in the CSF), are factors that must be highlighted before defining the causality of the association. Added to the two previous points is the sensitivity to the moment of the pandemic in which the article was produced. The beginning of an important vaccination campaign, in the midst of the growth of anti-vaccine groups, inspires caution when associating causality without the possibility of ruling out, through more elaborate tests, other causes. Finally, the level of evidence that a case report has in comparison to other scientific productions is highlighted. Then, for a reliable correlation between the SARS-CoV-2 vaccine and GBS, studies with a higher level of evidence are necessary, such as randomized clinical trials and systematic reviews.³

Furthermore, it is noteworthy that the delay between the onset of symptoms and diagnosis was due to the patient having interpreted the initial changes as of psychiatric origin, taking 2 months to seek the medical service of reference in the region. Thus, there is a consensus among us authors that the delay in diagnosis and treatment, as well highlighted by Finsterer et al., may have been one of the factors that led to worse outcome. The authors also emphasize that the findings of the patient's neurological physical examination are those described in the article, so, those not mentioned, such as the involvement of several pairs of cranial nerves, were not present.

Therefore, for all the reasons mentioned above and despite the interesting and pertinent comments made by Finsterer et al., the authors adopted a more cautious approach and, thus, defined the case as a temporal association, not necessarily a causal one.

None declared.

All authors are in agreement with the content of the manuscript. All authors participated in the data acquisition and analysis, and contributed to the drafting of the manuscript.

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