Moesin is a possible target molecule for cytomegalovirus-related Guillain-Barré syndrome
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- Cytomegalovirus infection in Guillain-Barré syndrome: a retrospective study in Brazil, Arquivos de Neuro-Psiquiatria, 79, 7, (607-611), (2021).https://doi.org/10.1590/0004-282x-anp-2020-0464
- Methodology for identification of new target molecules in neuroimmunological disorders, Clinical and Experimental Neuroimmunology, 12, 3, (202-207), (2021).https://doi.org/10.1111/cen3.12645
- A Guillain-Barré syndrome-associated SIGLEC10 rare variant impairs its recognition of gangliosides, Journal of Autoimmunity, 116, (102571), (2021).https://doi.org/10.1016/j.jaut.2020.102571
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We appreciate Miyaji et al.'s further comments on our study. [1] As described in our paper, anti-moesin antibodies are also found in patients with the paroxysmal nocturnal hemoglobulinuria type of acquired aplastic anemia. [2] The anti-moesin antibodies in these 2 diseases recognize distinct epitopes of the moesin protein. The antibody in aplastic anemia was reported to recognize a C-terminal part of moesin amino acid sequences. [2] However, amino acid sequence 'HRGMLR', analyzed by the BLAST program by comparing the sequences of moesin and CMV proteins in our study, was located at a different site from the C- terminal, and was listed as the candidate of immune target. Separately, we completely agree that an animal model of AIDP by immunization with moesin protein (peptide) is necessary to confirm the disease pathogenesis of CMV-related AIDP, and we would like to do so in the future.
1. Sawai S, Satoh M, Mori M, et al. Moesin is a possible target molecule for cytomegalovirus-related Guillain-Barre syndrome. Neurology 2014;83:113-117.
2. Takamatsu H, Feng X, Chuhjo T, et al. Specific antibodies to moesin, a membrane-cytoskeleton linker protein, are frequently detected in patients with acquired aplastic anemia. Blood. 2007;109:2514-2520.
For disclosures, contact the editorial office at [email protected].
We thank Dr. Sawai and colleagues for responding to our query. The presence of similar autoantibodies in aplastic anemia strongly suggests anti-moesin antibodies are unlikely to play a role in the development of Guillain-Barre syndrome. Sawai et al. described the amino acid sequences HRGMLR as common between cytomegalovirus and moesin. [1] To support the presence of molecular mimicry between cytomegalovirus and moesin, binding of patients' sera with the peptide HRGMLR should be demonstrated.
Previous studies demonstrated molecular mimicry between Campylobacter jejuni and GM1 or GD1a, and replicas of acute motor axonal motor neuropathy by active immunization of GM1 or passive transfer of anti-GM1 antibodies. [2-5] To prove the current hypothesis, it is important to produce an animal model of acute inflammatory demyelinating polyneuropathy by active immunization of the hexapeptides or passive transfer of the IgG antibodies to the peptides.
1. Sawai S, Satoh M, Mori M, et al. Moesin is a possible target molecule for cytomegalovirus-related Guillain-Barre syndrome. Neurology 2014;83:113-117.
2. Yuki N, Taki T, Inagaki F, et al. A bacterium lipopolysaccharide that elicits Guillain-Barre syndrome has a GM1 ganglioside-like structure. J Exp Med 1993;178:1771-1775.
3. Yuki N, Yamada M, Koga M, et al. Animal model of axonal Guillain-Barre syndrome induced by sensitization with GM1 ganglioside. Ann Neurol 2001;49:712-720.
4. Goodfellow JA, Bowes T, Sheikh K, et al. Overexpression of GD1a ganglioside sensitizes motor nerve terminals to anti-GD1a antibody-mediated injury in a model of acute motor axonal neuropathy. J Neurosci 2005;25:1620-1628.
5. Greenshields KN, Halstead SK, Zitman FMP, et al. The neuropathic potential of anti-GM1 autoantibodies is regulated by the local glycolipid environment in mice. J Clin Invest 2009;119:595-610.
For disclosures, please contact the editorial office at [email protected].
Miyaji et al. stated that in their Guillain-Barre syndrome cohort, anti- moesin antibodies were not detected by enzyme-linked immunosorbent assay. Our report showed positive anti-moesin antibodies in patients with cytomegalovirus-related Guillain-Barre syndrome by immunoblotting and immunocytochemistry. For proper comparison, the same methods should be used to validate previously reported findings. Results of antibody assays may not be identical by different assays such as enzyme-linked immunosorbent assay, and future studies are required.
Miyaji et al. also mentioned that moesin is an intracellular protein and thereby an unlikely immunological target molecule. Moesin classically links the cell membrane and cytoskeleton, and mediates the formation of microtubules and cell adhesion sites. [1] Several studies have reported that moesin is also detected on the cell surface of lymphocytes and macrophages by flow cytometry, indicating that moesin regulates cytokine production when activated by infection or inflammation. [2-4] Moreover, anti-moesin antibodies are detected in sera from patients with aplastic anemia. [5] Moesin is a possible target molecule for cytomegalovirus-related Guillain-Barre syndrome, as we indicated in our title.
1. Tsukita S, Yonemura S. Cortical actin organization: lessons from ERM (ezrin/radixin/moesin) proteins. J Biol Chem 1999;274:34507-34510.
2. Amar S, Oyaisu K, Li L, et al. Moesin: a potential LPS receptor on human monocytes. J Endotoxin Res 2001;7:281-286.
3. Iontcheva I, Amar S, Zawawi KH, et al. Role for moesin in lipopolysaccharide-stimulated signal transduction. Infect Immun 2004;72:2312-2320.
4. Takamatsu H, Espinoza JL, Lu X, et al. Anti-moesin antibodies in the serum of patients with aplastic anemia stimulate peripheral blood mononuclear cells to secrete TNF-alpha and IFN-gamma. J Immunol 2009;182:703-710.
5. Takamatsu H, Feng X, Chuhjo T, et al. Specific antibodies to moesin, a membrane-cytoskeleton linker protein, are frequently detected in patients with acquired aplastic anemia. Blood 2007;109:2514-2520.
For disclsoures, please contact the editorial office at [email protected].
Sawai et al. [1] reported moesin as a possible target molecule for cytomegalovirus-related Guillain-Barre syndrome, especially acute inflammatory demyelinating polyneuropathy (AIDP). We aimed to validate their observations in our cohort of patients with AIDP by enzyme-linked immunosorbent assay, which usually has a higher sensitivity than immunoblotting. None of the 41 patients with AIDP, including 8 cytomegalovirus-related AIDP patients, had IgG or IgM antibodies to moesin (unpublished data).
Deposition of activated complement components and membrane attack complex were observed along the outer surface of Schwann cells in the motor nerves of AIDP patients. [2] This finding suggested that target molecules are extracellular. Moesin along with ezrin and radixin were present as intracellular proteins. We believe that moesin is an unlikely target molecule for cytomegalovirus-related AIDP.
1. Sawai S, Satoh M, Mori M, et al. Moesin is a possible target molecule for cytomegalovirus-related Guillain-Barre syndrome. Neurology 2014;83:113-117.
2. Hafer-Macko CE, Sheikh KA, Li CY, et al. Immune attack on the Schwann cell surface in acute inflammatory demyelinating polyneuropathy. Ann Neurol 1996;39:625-635.
For disclosures, please contact the editorial office at [email protected].