Minimal immune determinants connect Zika virus, human Cytomegalovirus, and <i>Toxoplasma gondii</i> to microcephaly‐related human proteins

Lucchese, Guglielmo; Kanduc, Darja

doi:10.1111/aji.12608

Cited by 16 publications

(17 citation statements)

References 30 publications

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“…Recent studies have shown a close relationship between Zika virus infection and the occurrence of AIDP, but not AMAN 34. Interestingly, peptide sharing was reported among proteins of Zika virus, cytomegalovirus and the human peripheral nervous system 35 36. Axonal damage, conspicuous in four of our patients, may have occurred secondary to inflammation at the proximal nerve trunk 37.…”

Section: Discussionsupporting

confidence: 44%

Ultrastructural mechanisms of macrophage-induced demyelination in Guillain-Barré syndrome

Koike

Fukami

Nishi

et al. 2020

J Neurol Neurosurg Psychiatry

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ObjectiveTo describe the pathological features of Guillain-Barré syndrome focusing on macrophage-associated myelin lesions.MethodsLongitudinal sections of sural nerve biopsy specimens from 11 patients with acute inflammatory demyelinating polyneuropathy (AIDP) exhibiting macrophage-associated demyelinating lesions were examined using electron microscopy. A total of 1205 nodes of Ranvier were examined to determine the relationship of the macrophage-associated demyelinating lesions with the nodal regions. Additionally, immunohistochemical and immunofluorescent studies were performed to elucidate the sites of complement deposition.ResultsOverall, 252 macrophage-associated myelin lesions were identified in longitudinal sections. Of these, 40 lesions exhibited complete demyelination with no association with the lamellar structures of myelin. In 183 lesions, macrophage cytoplasm was located at internodes without association with the nodes of Ranvier or paranodes. In particular, these internodal lesions were more frequent in one patient (152 lesions). In the remaining 29 lesions, the involvement of nodal regions was obvious. Lesions involving nodal regions were more frequently observed than those involving internodes in four patients. Invasion of the macrophage cytoplasmic processes into the space between the paranodal myelin terminal loops and the axolemma from the nodes of Ranvier was observed in three of these patients. Immunostaining suggested complement deposition corresponding to putative initial macrophage-associated demyelinating lesions.ConclusionsThe initial macrophage-associated demyelinating lesions appeared to be located at internodes and at nodal regions. The sites at which the macrophages initiated phagocytosis of myelin might be associated with the location of complement deposition in certain patients with AIDP.

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Section: Discussionsupporting

confidence: 44%

Ultrastructural mechanisms of macrophage-induced demyelination in Guillain-Barré syndrome

Koike

Fukami

Nishi

et al. 2020

J Neurol Neurosurg Psychiatry

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“…We found that the brain weight of DPP6-KO mice was significantly lower than WT at 3 and 6 months (Figure 4E , insert, n = 15–28 per age, p = 0.0001, F (2,104) = 9.866, Two-way ANOVA). Studies indicate that the DPP6 gene is associated with microcephaly and mental retardation (Liao et al, 2013 ; Lucchese and Kanduc, 2017 ).…”

Section: Resultsmentioning

confidence: 99%

DPP6 Loss Impacts Hippocampal Synaptic Development and Induces Behavioral Impairments in Recognition, Learning and Memory

Lin

Murphy

Karlsson

et al. 2018

Front. Cell. Neurosci.

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DPP6 is well known as an auxiliary subunit of Kv4-containing, A-type K+ channels which regulate dendritic excitability in hippocampal CA1 pyramidal neurons. We have recently reported, however, a novel role for DPP6 in regulating dendritic filopodia formation and stability, affecting synaptic development and function. These results are notable considering recent clinical findings associating DPP6 with neurodevelopmental and intellectual disorders. Here we assessed the behavioral consequences of DPP6 loss. We found that DPP6 knockout (DPP6-KO) mice are impaired in hippocampus-dependent learning and memory. Results from the Morris water maze and T-maze tasks showed that DPP6-KO mice exhibit slower learning and reduced memory performance. DPP6 mouse brain weight is reduced throughout development compared with WT, and in vitro imaging results indicated that DPP6 loss affects synaptic structure and motility. Taken together, these results show impaired synaptic development along with spatial learning and memory deficiencies in DPP6-KO mice.

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“…More recently, Lucchese and Kanduc [40,41] suggested that the massive sharing of minimal epitopic determinants among pathogens -namely Zika virus, Epstein-Barr virus, Cytomegalovirus, Influenza virus, Campylobacter jejuni, and Mycoplasma pneumoniae, among others -and the consequent potential cross-reactivity might represent the molecular basis and mechanism by which different infections over time can irrevocably imprint the host immunological memory, thus leading to subsequent anamnestic, misled, immune responses. Said data [40,41] and the present ones add biochemical evidence in supporting the view that 'a cell, which has once produced antibody, is not only preempted to performing the same task again but does this on the slightest provocation by accepting what we may regard as not quite appropriate stimuli' [80].…”

Section: Resultsmentioning

confidence: 99%

Inter-Pathogen Peptide Sharing and the Original Antigenic Sin: Solving a Paradox

Kanduc¹,

Shoenfeld²

2018

TOIJ

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Aims:To analyse the peptide commonality among viral, bacterial, and protozoan pathogens, and the immunopathologic consequences in the human host.Methods:HPV16, HCMV,C. diphtheriae, B. pertussis, C. tetani, T. gondii,andT. cruziwere analysed for common amino acid sequences that are additionally shared with the human host. The pentapeptide, a minimal immune determinant in humoral and cellular immune recognition, was used as a measurement unit of the peptide similarity level. Molecular modeling was applied to compare the amino acid contexts containing common minimal determinants.Results:Twenty-nine pentapeptides were found to occur, even hundreds of times, throughout the analyzed pathogen proteomes as well as in the human proteome. Such vast peptide commonalities together with molecular modeling data support the possibility that a pre-existing immune response to a first pathogen can be boosted by a successive exposure to a second different pathogen,i.e., the primary response to a pathogen can be transformed into a secondary response to a previously encountered different pathogen. Two possible consequences emerge. Firstly, no responses might be elicited against the pathogen lastly encountered either by infection or active immunization, but reactions could occur only with the early sensitizing pathogen, which is no more present in the organism. Secondly, the immune response boosted by the pathogen lastly encountered will find a way out by cross-reacting with human proteins.Conclusion:This study might explain the “original antigenic sin” phenomenon described seven decades ago [Francis T. Jr. Ann Intern Med 1953;39:203], thus providing explanations for vaccine failures and offering possible clues for designing successful vaccines.

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Minimal immune determinants connect Zika virus, human Cytomegalovirus, and Toxoplasma gondii to microcephaly‐related human proteins

Cited by 16 publications

References 30 publications

Ultrastructural mechanisms of macrophage-induced demyelination in Guillain-Barré syndrome

Ultrastructural mechanisms of macrophage-induced demyelination in Guillain-Barré syndrome

DPP6 Loss Impacts Hippocampal Synaptic Development and Induces Behavioral Impairments in Recognition, Learning and Memory

Inter-Pathogen Peptide Sharing and the Original Antigenic Sin: Solving a Paradox

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