Tetanus Infection and Epilepsy – Implications for Autism and Schizophrenia

The Peptide Network between Tetanus Toxin and Human Proteins Associated with Epilepsy.

http://www.hindawi.com/journals/ert/2014/236309/

Abstract

Sequence matching analyses show that Clostridium tetani neurotoxin shares numerous pentapeptides (68, including multiple occurrences) with 42 human proteins that, when altered, have been associated with epilepsy.

Such a peptide sharing is higher than expected, nonstochastic, and involves tetanus toxin-derived epitopes that have been validated as immunopositive in the human host.

Of note, an unexpected high level of peptide matching is found in mitogen-activated protein kinase 10 (MK10), a protein selectively expressed in hippocampal areas.

On the whole, the data indicate a potential for cross-reactivity between the neurotoxin and specific epilepsy-associated proteins and may help evaluate the potential risk for epilepsy following immune responses induced by tetanus infection. Moreover, this study may contribute to clarifying the etiopathogenesis of the different types of epilepsy.

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From the full paper

“In the disease model examined here, that is, tetanus infection and epilepsy, the ample cross-reactivity platform between TT-derived epitopes and human epilepsy-associated antigens supports the hypothesis of an immune involvement in epilepsy.

As a matter of fact, all the 42 epilepsy-related proteins listed in Box 2 are potential targets of cross-reactions (see Table 1). Qualitatively, the peptide overlap occurs in human proteins canonically associated with epilepsy such as gamma-aminobutyric acid receptor subunit alpha-1 (GBRA1), gamma-aminobutyric acid type B receptor subunit 1 (GABR1), sodium channel protein subunits (SCN1A, SCN2A. SCN8A, and SCN9A), and calcium-activated potassium channel subunit alpha-1 (KCMA1) (Table 1).

Obviously, an immune attack against such epilepsy-associated proteins may cause alterations to neural structures and functions, especially when the neurodevelopmental intrauterine phase is considered. Being of nonsecondary importance, the nonstochastic character of the peptide overlap between TT and epilepsy-associated proteins (Figure 1) indicates that the potential cross-reactivity extent (and the associated risk of developing epilepsy and neurodevelopmental disorders) will increase with the number of anti-TT immune stimulations.

An additional relevant point is the “antigenic patchwork” shown in Table 1. Indeed, the potential peptide crossreactome involved in different extent and in different combinations of 42 epilepsy-associated proteins might help understand the complex neurobiological network that, once hit and perturbed, may underlie different epileptic forms [1–9].

Also, it has to be noted that Table 1 includes proteins such as CNTP2 or contactin-associated protein-like 2, RELN or reelin, and TSC1 or tuberous sclerosis 1 protein, which are also landmark antigens for autism and the associated impairment in communication/language skills and behaviors [78–81].

Hence, Table 1 may provide a mechanistic framework to allocate the occurrence of epilepsy, intellectual disability, and autism spectrum disorder in patients with tuberous sclerosis complex.

Likewise, data from Table 1 might contribute to answering a critical question in neuropsychopathology, that is, the coexistence of patients with combined schizophrenia and epilepsy [82–85].”

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Guglielmo Lucchese, Jean Pierre Spinosa, and Darja Kanduc, “The Peptide Network between Tetanus Toxin and Human Proteins Associated with Epilepsy,” Epilepsy Research and Treatment, vol. 2014, Article ID 236309, 11 pages, 2014. doi:10.1155/2014/236309

 

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This entry was posted in Autism, co-morbid, Environment, epilepsy, Immune System, Inflammation, Neurology, Physiology, Schizophrenia, Treatment. Bookmark the permalink.

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