83 results on '"Kanduc D"'
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2. Erratum to 'Why are we vaccinating children against COVID-19?' [Toxicol. Rep. 8C (2021) 1665–1684 / 1193] (Toxicology Reports (2021) 8 (1665–1684), (S221475002100161X), (10.1016/j.toxrep.2021.08.010))
- Author
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Kostoff, R.N. Calina, D. Kanduc, D. Briggs, M.B. Vlachoyiannopoulos, P. Svistunov, A.A. Tsatsakis, A.
- Abstract
The publisher wishes to clarify that Dr Aristidis Tsatsakis, the Editor-in-Chief of Toxicology Reports, was not involved in the peer-review of this article. Full responsibility for the editorial process for this article was delegated to the Handling Editor Dr Konstantinos Poulas. The publisher would like to apologise for any inconvenience caused. © 2021 The Author(s)
- Published
- 2021
3. The Guillain–Barrè peptide signatures: from Zika virus to Campylobacter, and beyond
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Lucchese G and Kanduc D
- Subjects
GBS-related human proteins ,Guillain-Barre syndrome (GBS) ,lcsh:QR1-502 ,lcsh:Microbiology ,Zika virus ,GBS-related pathogens: multiple crossreactivity - Abstract
Guglielmo Lucchese,1 Darja Kanduc2 1Brain Language Laboratory, Freie Universität Berlin, Berlin, Germany; 2Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy Abstract: Scientific attention has focused recently on the link between Guillain–Barrè syndrome (GBS) and Zika virus (ZIKV). Two related questions emerged: 1) what triggered the violent 2014 outbreak of a virus, which, first identified in 1947, had caused only a limited number of documented cases of human infection until 2007 and 2) which molecular mechanism(s) relate ZIKV active infection to GBS, an autoimmune inflammatory polyradiculoneuropathy. Capitalizing on the increased interest on ZIKV and hypothesizing the involvement of autoimmune mechanisms, we searched for minimal epitopic determinants shared between ZIKV and other GBS-related pathogens – namely, Epstein–Barr virus, human cytomegalovirus, influenza virus, Campylobacter jejuni, and Mycoplasma pneumoniae, among others – and human proteins that, when altered, have been associated with myelin disorders and axonopathies. We report a considerable peptide matching that links GBS-related pathogens to human proteins related to myelin disorders and axonopathies. Crucially, the shared pentapeptides repeatedly occur throughout numerous epitopes validated as immunopositive by a conspicuous scientific literature. The data support a scenario where multiple different infections over time and resulting multiple cross-reactions may contribute to the pathogenesis of GBS. In practice, previous infection(s) might create immunologic memory able to trigger uncontrolled hyperimmunogenicity during a successive pathogen exposure. ZIKV pandemic appears to be an exemplar model for a proof-of-concept of such multiple cross-reactivity mechanism. Keywords: peptide sharing, GBS-related human proteins, GBS-related pathogens, multiple cross reactivity, hyperimmunogenicity
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- 2017
4. Cell Death: apoptosis versus necrosis
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KANDUC D., SERPICO R, SINIGALLIA E, SINHA A, NATALE C, SANTACROCE R, DI CORCIA M, LUCCHESE A, DINI L., PANI P, SANTACROCE S, SIMONE S, BUCCI R, FARBER E., DINI, Luciana, Kanduc, D, Mittelman, A, Serpico, Rosario, Sinigaglia, E, Sinha, Aa, Natale, C, Santacroce, R, DI CORCIA, Mg, Lucchese, Alberta, Dini, L, Pani, P, Santacroce, S, Simone, S, Bucci, R, Farber, E., Kanduc, D., Dini, Luciana, Serpico, R, Sinigallia, E, Sinha, A, DI CORCIA, M, Lucchese, A, and Dini, L.
- Published
- 2002
5. Peptide Sharing Between Influenza A H1N1 Hemagglutinin and Human Axon Guidance Proteins
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Lucchese, G., primary, Capone, G., additional, and Kanduc, D., additional
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- 2013
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6. Peptide mimotopes of oncoproteins as therapeutic agents in breast cancer
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Ashok, B., primary, David, L., additional, Chen, Y., additional, Garikapaty, V., additional, Chander, B., additional, Kanduc, D., additional, Mittelman, A., additional, and Tiwari, R., additional
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- 2003
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7. Phosphate transport in mitochondria action of mersalyl on the binding and transport of inorganic phosphate
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Papa, S., primary, Kanduc, D., additional, and Lofrumento, N.E., additional
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- 1973
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8. Pentapeptide overlapping between human immunodeficiency viruses and Home sapiens proteomes is higher than 90%
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Kanduc Darja
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Immunologic diseases. Allergy ,RC581-607 - Published
- 2009
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9. The oligodeoxynucleotide sequences corresponding to never-expressed peptide motifs are mainly located in the non-coding strand
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Bickis Mik, Trost Brett, Fasano Candida, Novello Giuseppe, Capone Giovanni, Kusalik Anthony, and Kanduc Darja
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Computer applications to medicine. Medical informatics ,R858-859.7 ,Biology (General) ,QH301-705.5 - Abstract
Abstract Background We study the usage of specific peptide platforms in protein composition. Using the pentapeptide as a unit of length, we find that in the universal proteome many pentapeptides are heavily repeated (even thousands of times), whereas some are quite rare, and a small number do not appear at all. To understand the physico-chemical-biological basis underlying peptide usage at the proteomic level, in this study we analyse the energetic costs for the synthesis of rare and never-expressed versus frequent pentapeptides. In addition, we explore residue bulkiness, hydrophobicity, and codon number as factors able to modulate specific peptide frequencies. Then, the possible influence of amino acid composition is investigated in zero- and high-frequency pentapeptide sets by analysing the frequencies of the corresponding inverse-sequence pentapeptides. As a final step, we analyse the pentadecamer oligodeoxynucleotide sequences corresponding to the never-expressed pentapeptides. Results We find that only DNA context-dependent constraints (such as oligodeoxynucleotide sequence location in the minus strand, introns, pseudogenes, frameshifts, etc.) provide a coherent mechanistic platform to explain the occurrence of never-expressed versus frequent pentapeptides in the protein world. Conclusions This study is of importance in cell biology. Indeed, the rarity (or lack of expression) of specific 5-mer peptide modules implies the rarity (or lack of expression) of the corresponding n-mer peptide sequences (with n < 5), so possibly modulating protein compositional trends. Moreover the data might further our understanding of the role exerted by rare pentapeptide modules as critical biological effectors in protein-protein interactions.
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- 2010
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10. Preliminary data on Pemphigus vulgaris treatment by a proteomics-defined peptide: a case report
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Mittelman Abraham, Serpico Rosario, Favia Gianfranco, Lucchese Alberta, Bonamonte Domenico, Angelini Giovanni, Simone Simone, Sinha Animesh A, and Kanduc Darja
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Medicine - Abstract
Abstract Background Although described by Hippocrates in 400 B.C., pemphigus disease still needs a safe therapeutical approach, given that the currently used therapies (i.e. corticosteroids and immunosuppressive drugs) often provoke collateral effects. Here we present preliminary data on the possible use of a proteomics derived desmoglein peptide which appears promising in halting disease progression without adverse effects. Methods The low-similarity Dsg349–60REWVKFAKPCRE peptide was topically applied for 1 wk onto a lesion in a patient with a late-stage Pemphigus vulgaris (PV) complicated by diabetes and cataract disease. The peptide was applied as an adjuvant in combination with the standard corticosteroid-based immunosuppressive treatment. Results After 1 wk, the treated PV eroded lesion appeared dimensionally reduced and with an increased rate of re-epithelization when compared to adjacent non-treated lesions. Short-term benefits were: decrease of anti-Dsg antibody titer and reduction of the corticosteroid dosage. Long-term benefits: after two years following the unique 1-wk topical treatment, the decrease of anti-Dsg antibody titer persists. The patient is still at the low cortisone dosage. Adverse effects: no adverse effect could be monitored. Conclusion With the limits inherent to any preliminary study, this case report indicates that topical treatment with Dsg349–60REWVKFAKPCRE peptide may represent a feasible first step in the search for a simple, effective and safe treatment of PV.
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- 2006
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11. Proteomic definition of a desmoglein linear determinant common to Pemphigus vulgaris and Pemphigus foliaceous
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Sinha Animesh A, Serpico Rosario, Tessitore Luciana, Mittelman Abraham, Lucchese Alberta, and Kanduc Darja
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Medicine - Abstract
Abstract Background A number of autoimmune diseases have been clinically and pathologically characterized. In contrast, target antigens have been identified only in a few cases and, in these few cases, the knowledge of the exact epitopic antigenic sequence is still lacking. Thus the major objective of current work in the autoimmunity field is the identification of the epitopic sequences that are related to autoimmune reactions. Our labs propose that autoantigen peptide epitopes able to evoke humoral (auto)immune response are defined by the sequence similarity to the host proteome. The underlying scientific rationale is that antigen peptides acquire immunoreactivity in the context of their proteomic similarity level. Sequences uniquely owned by a protein will have high potential to evoke an immune reaction, whereas motifs with high proteomic redundancy should be immunogenically silenced by the tolerance phenomenon. The relationship between sequence redundancy and peptide immunoreactivity has been successfully validated in a number of experimental models. Here the hypothesis has been applied to pemphigus diseases and the corresponding desmoglein autoantigens. Methods Desmoglein 3 sequence similarity analysis to the human proteome followed by dot-blot/NMR immunoassays were carried out to identify and validate possible epitopic sequences. Results Computational analysis led to identifying a linear immunodominant desmoglein-3 epitope highly reactive with the sera from Pemphigus vulgaris as well as Pemphigus foliaceous. The epitopic peptide corresponded to the amino acid REWVKFAKPCRE sequence, was located in the extreme N-terminal region (residues 49 to 60), and had low redundancy to the human proteome. Sequence alignment showed that human desmoglein 1 and 3 share the REW-KFAK–RE sequence as a common motif with 75% residue identity. Conclusion This study 1) validates sequence redundancy to autoproteome as a main factor in shaping desmoglein peptide immunogenicity; 2) offers a molecular mechanicistic basis in analyzing the commonality of autoimmune responses exhibited by the two forms of pemphigus; 3) indicates possible peptide-immunotherapeutical approaches for pemphigus diseases.
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- 2006
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12. Epitope definition by proteomic similarity analysis: identification of the linear determinant of the anti-Dsg3 MAb 5H10
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Kanduc Darja, Lin Mong-Shang, Mittelman Abraham, Lucchese Alberta, and Sinha Animesh A
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Epitope mapping ,Computational biology ,Proteomics ,Desmoglein 3 ,Pemphigus vulgaris ,Medicine - Abstract
Abstract Background Walking along disease-associated protein sequences in the search for specific segments able to induce cellular immune response may direct clinical research towards effective peptide-based vaccines. To this aim, we are studying the targets of the immune response in autoimmune diseases by applying the principle of non-self-discrimination as a driving concept in the identification of the autoimmunogenic peptide sequences. Methods Computer-assisted proteomic analysis of the autoantigen protein sequence and dot-blot/NMR immunoassays are applied to the prediction and subsequent validation of the epitopic sequences. Results Using the experimental model Pemphigus vulgaris/desmoglein 3, we have identified the antigenic linear determinant recognized by MAb 5H10, a monoclonal antibody raised against the extracellular domain of human desmoglein-3. The computer-assisted search for the Dsg3 epitope was conducted by analyzing the similarity level to the mouse proteome of the human desmoglein protein sequence. Dot-blot immunoassay analyses mapped the epitope within the sequence Dsg349–60 REWVKFAKPCRE, which shows low similarity to the mouse proteome. NMR spectroscopy analyses confirmed the specificity of MAb 5H10 for the predicted epitope. Conclusions This report promotes the concept that low level of sequence similarity to the host's proteome may modulate peptide epitopicity.
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- 2004
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13. Proposing low-similarity peptide vaccines against Mycobacterium tuberculosis.
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Lucchese G, Stufano A, and Kanduc D
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Using the currently available proteome databases and based on the concept that a rare sequence is a potential epitope, epitopic sequences derived from Mycobacterium tuberculosis were examined for similarity score to the proteins of the host in which the epitopes were defined. We found that: (i) most of the bacterial linear determinants had peptide fragment(s) that were rarely found in the host proteins and (ii) the relationship between low similarity and epitope definition appears potentially applicable to T-cell determinants. The data confirmed the hypothesis that low-sequence similarity shapes or determines the epitope definition at the molecular level and provides a potential tool for designing new approaches to prevent, diagnose, and treat tuberculosis and other infectious diseases. [ABSTRACT FROM AUTHOR]
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- 2010
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14. Sjögren’s Syndrome Associated with Chikungunya Infection: A Case Report
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Alberta Lucchese, Jozélio Freire de Carvalho, Darja Kanduc, Yehuda Shoenfeld, Felipe Freire Silva, Amir Tanay, de Carvalho, J. F., Kanduc, D., da Silva, F. F., Tanay, A., Lucchese, A., and Shoenfeld, Y.
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medicine.medical_specialty ,Anti-nuclear antibody ,Case Report ,Autoimmunity ,medicine.disease_cause ,Rheumatology ,Arboviruse ,Internal medicine ,medicine ,Immunology and Allergy ,Chikungunya ,Autoantibodies ,business.industry ,Autoantibody ,virus diseases ,Hydroxychloroquine ,medicine.disease ,Autoantibodie ,Sjögren syndrome ,Rheumatoid arthritis ,Immunology ,Polyarthritis ,Chikungunya infection ,business ,Arboviruses ,Molecular mimicry ,medicine.drug - Abstract
Chikungunya virus (CHIKV) infection is caused by an arbovirus prevalent in various parts of the world. The virus can induce autoantibodies and rheumatic diseases, such as rheumatoid arthritis and spondylarthritis. However, until now, no case of Sjögren syndrome (SS) was described associated with CHIKV. In this article, we describe a 49-year-old female with polyarthralgia and a temporary rash on her trunk and arms. Her physical examination showed polyarthritis of her ankles and wrists. Serologies for CHIKV were interpreted as positive with IgM 6.5 (normal range < 0.8) and negative for IgG. Antinuclear antibodies were positive at a titer of 1:640 as well as anti-Ro/SS-A. The diagnosis of subacute CHIKV infection was determined. The Schirmer test, Rose Bengal, and salivary scintigraphy were positive and the diagnosis of SS was confirmed. She was treated with hydroxychloroquine, methotrexate, and a single dose of betamethasone depot. This is the first report on CHIKV associated with SS. Sequence analysis of the CHIKV proteome versus SS autoantigens showed an extensive peptide sharing between the virus and numerous SS autoantigens, thus supporting the hypothesis that autoimmune cross-reactivity might causally link CHIKV to SS.
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- 2021
15. Molecular signatures of basal cell carcinoma susceptibility and pathogenesis: A genomic approach
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Qiang Hu, Animesh A. Sinha, Song Liu, Ankit Gor, Meena Katdare, Elizabeth Rose Heller, Darja Kanduc, Dan Wang, Alberta Lucchese, Heller, Er, Gor, A, Wang, D, Hu, Q, Lucchese, Alberta, Kanduc, D, Katdare, M, Liu, S, and Sinha, Aa
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Aged, 80 and over ,Male ,Regulation of gene expression ,Genetics ,Cancer Research ,Microarray ,Carcinogenesis ,Microarray analysis techniques ,Gene Expression Profiling ,Gene signature ,Biology ,Lipid Metabolism ,Gene Expression Regulation, Neoplastic ,PPAR gamma ,Gene expression profiling ,Oncology ,Carcinoma, Basal Cell ,Transforming Growth Factor beta ,Humans ,Hedgehog Proteins ,Human genome ,Tumor Suppressor Protein p53 ,DNA microarray ,Gene ,Aged - Abstract
Gene expression profiling can be useful for phenotypic classification, investigation of functional pathways, and to facilitate the search for disease risk genes through the integration of transcriptional data with available genomic information. To enhance our understanding of the genetic and molecular basis of basal cell carcinoma (BCC) we performed global gene expression analysis to generate a disease-associated transcriptional profile. A gene signature composed of 331 differentially expressed genes (DEGs) was generated from comparing 4 lesional and 4 site-matched control samples using Affymetrix Human Genome U95A microarrays. Hierarchical clustering based on the obtained gene signature separated the samples into their corresponding phenotype. Pathway analysis identified several significantly overrepresented pathways including PPAR-γ signaling, TGF-β signaling and lipid metabolism, as well as confirmed the importance of SHH and p53 in the pathogenesis of BCC. Comparison of our microarray data with previous microarray studies revealed 13 DEGs overlapping in 3 studies. Several of these overlapping genes function in lipid metabolism or are components of the extracellular matrix, suggesting the importance of these and related pathways in BCC pathogenesis. BCC-associated DEGs were mapped to previously reported BCC susceptibility loci including 1p36, 1q42, 5p13.3, 5p15 and 12q11-13. Our analysis also revealed transcriptional 'hot spots' on chromosome 5 which help to confirm (5p13 and 5p15) and suggest novel (5q11.2-14.3, 5q22.1-23.3 and 5q31-35.3) disease susceptibility loci/regions. Integrating microarray analyses with reported genetic information helps to confirm and suggest novel disease susceptibility loci/regions. Identification of these specific genomic and/or transcriptional targets may lead to novel diagnostic and therapeutic modalities.
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- 2013
16. Proteomic definition of a desmoglein linear determinant common to Pemphigus vulgaris and Pemphigus foliaceous
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Luciana Tessitore, Rosario Serpico, Abraham Mittelman, Animesh A. Sinha, Alberta Lucchese, Darja Kanduc, Lucchese, Alberta, Mittelman, A, Tessitore, L, Serpico, Rosario, Sinha, Aa, and Kanduc, D.
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education.field_of_study ,integumentary system ,business.industry ,Research ,lcsh:R ,Pemphigus vulgaris ,lcsh:Medicine ,Sequence alignment ,General Medicine ,Computational biology ,medicine.disease ,Desmoglein ,General Biochemistry, Genetics and Molecular Biology ,Epitope ,Pemphigus ,Desmoglein 1 ,Desmoglein 3 ,Immunology ,medicine ,Human proteome project ,business ,education - Abstract
Background A number of autoimmune diseases have been clinically and pathologically characterized. In contrast, target antigens have been identified only in a few cases and, in these few cases, the knowledge of the exact epitopic antigenic sequence is still lacking. Thus the major objective of current work in the autoimmunity field is the identification of the epitopic sequences that are related to autoimmune reactions. Our labs propose that autoantigen peptide epitopes able to evoke humoral (auto)immune response are defined by the sequence similarity to the host proteome. The underlying scientific rationale is that antigen peptides acquire immunoreactivity in the context of their proteomic similarity level. Sequences uniquely owned by a protein will have high potential to evoke an immune reaction, whereas motifs with high proteomic redundancy should be immunogenically silenced by the tolerance phenomenon. The relationship between sequence redundancy and peptide immunoreactivity has been successfully validated in a number of experimental models. Here the hypothesis has been applied to pemphigus diseases and the corresponding desmoglein autoantigens. Methods Desmoglein 3 sequence similarity analysis to the human proteome followed by dot-blot/NMR immunoassays were carried out to identify and validate possible epitopic sequences. Results Computational analysis led to identifying a linear immunodominant desmoglein-3 epitope highly reactive with the sera from Pemphigus vulgaris as well as Pemphigus foliaceous. The epitopic peptide corresponded to the amino acid REWVKFAKPCRE sequence, was located in the extreme N-terminal region (residues 49 to 60), and had low redundancy to the human proteome. Sequence alignment showed that human desmoglein 1 and 3 share the REW-KFAK–RE sequence as a common motif with 75% residue identity. Conclusion This study 1) validates sequence redundancy to autoproteome as a main factor in shaping desmoglein peptide immunogenicity; 2) offers a molecular mechanicistic basis in analyzing the commonality of autoimmune responses exhibited by the two forms of pemphigus; 3) indicates possible peptide-immunotherapeutical approaches for pemphigus diseases.
- Published
- 2006
17. Preliminary data on Pemphigus vulgaris treatment by a proteomics-defined peptide: a case report
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Rosario Serpico, Animesh A. Sinha, Abraham Mittelman, Domenico Bonamonte, Simone Simone, Alberta Lucchese, Giovanni Angelini, Gianfranco Favia, Darja Kanduc, Angelini, G, Bonamonte, D, Lucchese, Alberta, Favia, G, Serpico, Rosario, Mittelman, A, Simone, S, Sinha, Aa, and Kanduc, D.
- Subjects
Pathology ,medicine.medical_specialty ,business.industry ,Research ,lcsh:R ,Pemphigus vulgaris ,Disease progression ,lcsh:Medicine ,General Medicine ,Disease ,medicine.disease ,Bioinformatics ,Proteomics ,Desmoglein ,General Biochemistry, Genetics and Molecular Biology ,Pemphigus ,Peptide vaccine ,medicine ,business ,Adverse effect - Abstract
Background Although described by Hippocrates in 400 B.C., pemphigus disease still needs a safe therapeutical approach, given that the currently used therapies (i.e. corticosteroids and immunosuppressive drugs) often provoke collateral effects. Here we present preliminary data on the possible use of a proteomics derived desmoglein peptide which appears promising in halting disease progression without adverse effects. Methods The low-similarity Dsg349–60REWVKFAKPCRE peptide was topically applied for 1 wk onto a lesion in a patient with a late-stage Pemphigus vulgaris (PV) complicated by diabetes and cataract disease. The peptide was applied as an adjuvant in combination with the standard corticosteroid-based immunosuppressive treatment. Results After 1 wk, the treated PV eroded lesion appeared dimensionally reduced and with an increased rate of re-epithelization when compared to adjacent non-treated lesions. Short-term benefits were: decrease of anti-Dsg antibody titer and reduction of the corticosteroid dosage. Long-term benefits: after two years following the unique 1-wk topical treatment, the decrease of anti-Dsg antibody titer persists. The patient is still at the low cortisone dosage. Adverse effects: no adverse effect could be monitored. Conclusion With the limits inherent to any preliminary study, this case report indicates that topical treatment with Dsg349–60REWVKFAKPCRE peptide may represent a feasible first step in the search for a simple, effective and safe treatment of PV.
- Published
- 2006
18. Possible association between HPV16 E7 protein level and cytokeratin 19
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Alberta Lucchese, Lorenzo Lo Muzio, Gianfranco Favia, Rosario Serpico, Darja Kanduc, Favia, G, Kanduc, D, LO MUZIO, L, Lucchese, Alberta, and Serpico, Rosario
- Subjects
Keratinocytes ,Cancer Research ,viruses ,Papillomavirus E7 Proteins ,Uterine Cervical Neoplasms ,Biology ,medicine.disease_cause ,Genome ,Virus ,Cytokeratin ,Viral life cycle ,Translational regulation ,medicine ,Humans ,RNA, Messenger ,Papillomaviridae ,Messenger RNA ,Gene Expression Profiling ,Keratin-7 ,Zinc Fingers ,Oncogene Proteins, Viral ,Virology ,Gene Expression Regulation, Neoplastic ,Oncology ,Cancer research ,Carcinoma, Squamous Cell ,Keratins ,Female ,Viral disease ,Carcinogenesis ,Transcription Factors - Abstract
The mechanisms employed by human papillomaviruses (HPVs) to control the replication of the viral genome and the expression of the viral genes are extremely complex and further complicated by the fact that the viral life cycle is intricately tied to the differentiation program of its host epithelial tissue. Indeed, HPV-induced immortalization of keratinocytes and disruption of the normal cytokeratin (CK) expression pattern progress pari passu during the stepwise process that preludes to squamous cell carcinoma. In our study, we have analyzed the interaction occurring between HPV type 16 E7 mRNA and the intermediate cytokeratin filaments 7 and 19 and report data in favor of a possible association between HPV16 E7 protein level and CK19. © 2004 Wiley-Liss, Inc.
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- 2004
19. Enhanced expression of initiator TRNA(Met) in human gastric and colorectal carcinoma
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Costanzo Natale, Maria Grazia di Corcia, Alberta Lucchese, Darja Kanduc, Kanduc, D, GRAZIA DI CORCIA, M, Lucchese, Alberta, and Natale, C.
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RNA, Transfer, Met ,Colorectal cancer ,Clinical Biochemistry ,Population ,Biology ,medicine.disease_cause ,Biochemistry ,RNA, Transfer ,Stomach Neoplasms ,Gene expression ,Genetics ,medicine ,Protein synthesis initiation ,Humans ,RNA, Neoplasm ,education ,Molecular Biology ,Carcinogen ,Chromatography, High Pressure Liquid ,education.field_of_study ,Cell growth ,Cell Biology ,medicine.disease ,Cell biology ,Transfer RNA ,Carcinogenesis ,Colorectal Neoplasms - Abstract
Transfer RNA isoaccepting species are differentially expressed at different times during development, differentiation, growth, aging, and carcinogenesis processes. It has been suggested that alterations in tRNA patterns might be mechanistically important in modulating gene expression during the various physiological/pathological cellular stages. As part of a study to investigate the possible mechanisms by which alterations of translational machinery can start and/or sustain carcinogenic cell proliferation, in this communication we report analysis of tRNA distribution in two gastro-intestinal human tumors. The qualitative and quantitative data obtained for cellular tRNA distribution put into evidence a shift in the tRNA population with increased level of initiator tRNA(Met) in the malignant tissues. This observation confirms previous data obtained on experimental carcinogenesis models and suggests the possibility of specific involvement of tRNA changes in protein synthesis initiation during tumorigenesis.
- Published
- 1998
20. Sequence uniqueness as a molecular signature of HIV-1-derived B-cell epitopes
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Alberta Lucchese, Yehuda Shoenfeld, Vito Crincoli, Rosario Serpico, Darja Kanduc, Lucchese, Alberta, Serpico, Rosario, Crincoli, V, Shoenfeld, Y, and Kanduc, D.
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Proteomics ,Mutation rate ,Immunology ,Computational biology ,Antibodies ,Epitope ,Mice ,Retrovirus ,Antibody Specificity ,Sequence Analysis, Protein ,Animals ,Humans ,Immunology and Allergy ,Amino Acid Sequence ,Databases, Protein ,Peptide sequence ,AIDS Vaccines ,Pharmacology ,Sequence Homology, Amino Acid ,biology ,Immunogenicity ,biology.organism_classification ,Vaccine therapy ,Vaccination ,Drug Design ,Proteome ,HIV-1 ,Epitopes, B-Lymphocyte ,Sequence Alignment - Abstract
The complex pathophysiology of human immunodeficiency virus (HIV) infection and the relatively high mutation rate of the retrovirus make it challenging to design effective anti-HIV vaccines. Several attempts have been made during the last decades to elucidate the enigmatic immunology of HIV infection and to predict potential immunogenic peptides for active vaccination using bioinformatic analysis methods. The results obtained to date to address this important problem are scarce. In this study, we exploit available HIV databases and analyse previously characterized HIV-encoded linear B-cell epitopes for their amino acid sequence similarity to the human or murine host proteome. We obtained further documentation that the HIV-derived antibody-targeted sequences mostly coincide with peptide areas rarely shared with the host proteins. In toto, our past and present data give clear-cut support to the statement that low-similarity to the host proteome is a major mechanism in defining viral peptide immunogenicity and indicate a possible way for inducing effective, high-titer, and non-cross-reactive antibodies to be used in anti-HIV vaccine therapy.
21. Interkeratin peptide-protein interactions that promote HPV16 E7 gene expression
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Rosario Serpico, Darja Kanduc, Agostino Guida, C Scully, Vito Crincoli, Alberta Lucchese, Lucchese, Alberta, Serpico, Rosario, Guida, A, Crincoli, V, Scully, C, and Kanduc, D.
- Subjects
Gene Expression Regulation, Viral ,Reticulocytes ,Papillomavirus E7 Proteins ,Immunology ,Intermediate filament cytoskeleton ,Electrophoretic Mobility Shift Assay ,Biology ,medicine.disease_cause ,Transfection ,Gene product ,Cytokeratin ,Mice ,Cell Line, Tumor ,Gene expression ,medicine ,Immunology and Allergy ,Animals ,Humans ,Neoplastic transformation ,RNA, Messenger ,RNA, Small Interfering ,Pharmacology ,Messenger RNA ,virus diseases ,3T3 Cells ,female genital diseases and pregnancy complications ,Cell biology ,Codon usage bias ,Protein Biosynthesis ,Keratins ,Rabbits ,Carcinogenesis ,Protein Binding - Abstract
Human papillomavirus (HPV) 16 E7 gene product encodes the major transforming activity of the virus so as to induce neoplastic transformation. Continued expression of HPV16 E7 protein is required for both the establishment and maintenance of the transformed cellular phenotype. Therefore, understanding of the molecular and biochemical factors leading to the expression of E7 protein is important in relation to HPV-associated diseases. Previously, we identified a rare codon usage and a specific interaction between cytokeratin (CK) 7 and HPV16 E7 mRNA as factors modulating HPV16 E7 expression. In the present study we report that CK19, a biochemical marker of squamous oral and cervical cancer carcinogenesis, promotes the expression of HPV16 E7 oncoprotein by binding to the CK792–97SEQIKA peptide. These findings shed light on the dynamic functionality of the intermediate filament cytoskeleton, open new perspectives for investigating the role of CKs in controlling HPV16 E7 expression, and suggest new therapeutic avenues for HPV-associated carcinomas.
22. On the Pentapeptide as the Measurement Unit in Immunology.
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Kanduc D
- Abstract
This communication concerns a crucial query in immunology, that is, the dimension of an epitope. The issue has essential implications in vaccine formulations., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)
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- 2024
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23. Molecular Mimicry between Meningococcal B Factor H-Binding Protein and Human Proteins.
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Kanduc D
- Abstract
This study calls attention on molecular mimicry and the consequent autoimmune cross reactivity as the molecular mechanism that can cause adverse events following meningococcal B vaccination and warns against active immunizations based on entire antigen., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)
- Published
- 2023
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24. Epigenetics of Hypogonadotropic Hypogonadism: Molecular Mimicry between Severe Acute Respiratory Syndrome Coronavirus 2 and KISSR.
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Kanduc D
- Abstract
This study analyzed KISS1 and its receptor KISSR for peptide sharing with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was found that SARS-CoV-2 shares numerous minimal immune pentapeptide determinants with KISSR only. The peptide sharing has a high immunologic potential since almost all the common peptides are present in 101 SARS-CoV-2-derived immunoreactive epitopes. Data are in favor of configuring molecular mimicry as an epigenetic factor that can alter KISSR thus causing the hypogonadotropic hypogonadism syndrome with which altered KISSR associates., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)
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- 2023
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25. Exposure to SARS-CoV-2 and Infantile Diseases.
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Kanduc D
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Background and Aim Immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in newborns and children after prophylactic immunization is currently a relevant research topic. The present study analyzes the issue by examining the possibility that the anti-SARS-CoV-2 immune responses are not uniquely directed against the virus but can-via molecular mimicry and the consequent cross-reactivity-also hit human proteins involved in infantile diseases. Methods Human proteins that-if altered-associate with infantile disorders were searched for minimal immune pentapeptide determinants shared with SARS-CoV-2 spike glycoprotein (gp). Then, the shared pentapeptides were analyzed for immunologic potential and immunologic imprinting phenomena. Results Comparative sequence analysis shows that: (1) numerous pentapeptides (namely, 54) are common to SARS-CoV-2 spike gp and human proteins that, when altered, are linked to infantile diseases; (2) all the shared peptides have an immunologic potential since they are present in experimentally validated SARS-CoV-2 spike gp-derived epitopes; and (3) many of the shared peptides are also hosted in infectious pathogens to which children can have already been exposed, thus making immunologic imprint phenomena feasible. Conclusion Molecular mimicry and the consequent cross-reactivity can represent the mechanism that connects exposure to SARS-CoV-2 and various pediatric diseases, with a fundamental role of the immunologic memory and the history of the child's infections in determining and specifying the immune response and the pathologic autoimmune sequela., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)
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- 2023
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26. Molecular Mimicry between Respiratory Syncytial Virus F Antigen and the Human Proteome.
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Kanduc D
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This study examined respiratory syncytial virus (RSV) F glycoprotein (gp) antigen for molecular mimicry with the human proteome. It was found that the viral antigen presents an impressive number of pentapeptides (namely, 525 out of 570) in common with the human proteome, with viral sequences widely and repeatedly distributed among 3,762 human proteins implicated in crucial fundamental cellular functions. The data can have implications for anti-RSV vaccines. Indeed, the high level of molecular mimicry can lead to cross-reactivity and autoimmunity, and invites to follow safer vaccinal protocols based on pentapeptide sequences uniquely present in the viral antigen., Competing Interests: Conflicts of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)
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- 2023
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27. Modifiable contributing factors to COVID-19: A comprehensive review.
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Kostoff RN, Briggs MB, Kanduc D, Dewanjee S, Kandimalla R, Shoenfeld Y, Porter AL, and Tsatsakis A
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- Humans, SARS-CoV-2, Inflammation, Immune System, COVID-19
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The devastating complications of coronavirus disease 2019 (COVID-19) result from an individual's dysfunctional immune response following the initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Multiple toxic stressors and behaviors contribute to underlying immune system dysfunction. SARS-CoV-2 exploits the dysfunctional immune system to trigger a chain of events ultimately leading to COVID-19. The current study identifies eighty immune system dysfunction-enabling toxic stressors and behaviors (hereafter called modifiable contributing factors (CFs)) that also link directly to COVID-19. Each CF is assigned to one of the five categories in the CF taxonomy shown in Section 3.3.: Lifestyle (e.g., diet, substance abuse); Iatrogenic (e.g., drugs, surgery); Biotoxins (e.g., micro-organisms, mycotoxins); Occupational/Environmental (e.g., heavy metals, pesticides); Psychosocial/Socioeconomic (e.g., chronic stress, lower education). The current study shows how each modifiable factor contributes to decreased immune system capability, increased inflammation and coagulation, and increased neural damage and neurodegeneration. It is unclear how real progress can be made in combatting COVID-19 and other similar diseases caused by viral variants without addressing and eliminating these modifiable CFs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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- 2023
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28. The Role of Codon Usage, tRNA Availability, and Cell Proliferation in EBV Latency and (Re)Activation.
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Kanduc D
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Epstein-Barr nuclear antigen 1 (EBNA1) protein synthesis is inhibited during Epstein-Barr virus (EBV) latency and is resumed in EBV (re)activation. In analyzing the molecular mechanisms underpinning the translation of EBNA1 in the human host, this article deals with two orders of data. First, it shows that the heavily biased codon usage of the EBNA1 open reading frame cannot be translated due to its noncompliance with the human codon usage pattern and the corresponding tRNA pool. The EBNA1 codon bias resides in the sequence composed exclusively of glycine and alanine, i.e., the Gly-Ala repeat (GAR). Removal of the nucleotide sequence coding for GAR results in an EBNA1 codon usage pattern with a lower codon bias, thus conferring translatability to EBNA1. Second, the data bring cell proliferation to the fore as a conditio sine qua non for qualitatively and quantitatively modifying the host's tRNA pool as required by the translational needs of EBNA1, thus enabling viral reactivation. Taken together, the present work provides a biochemical mechanism for the pathogen's shift from latency to (re)activation and confirms the role of human codon usage as a first-line tool of innate immunity in inhibiting pathogens' expression. Immunologically, this study cautions against using codon optimization and proliferation-inducing substances such as glucocorticoids and adjuvants, which can (re)activate the otherwise quiescent, asymptomatic, and innocuous EBV infection. Lastly, the data pose the question whether the causal pathogenic role attributed to EBV should instead be ascribed to the carcinogenesis-associated cellular proliferation., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)
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- 2022
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29. SARS-CoV-2: The Self-Nonself Issue and Diagnostic Tests.
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Kanduc D
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Objective At present, false negatives/positives have been reported in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostics. Searching for the molecular basis of such tests' unreliability, this study aimed at defining how specific are the sequences used in serological and polymerase chain reaction (PCR) tests to detect SARS-CoV-2. Materials and Methods Analyses were performed on the leading SARS-CoV-2 biomarker spike glycoprotein (gp). Sharing of peptide sequences between the spike antigen and the human host was analyzed using the Peptide Search program from Uniprot database. Sharing of oligonucleotide sequences was investigated using the nucleotide Basic Local Alignment Search Tool (BLASTn) from National Center for Biotechnology Information (NCBI). Results Two main points stand out: (1) a massive pentapeptide sharing exists between the spike gp and the human proteome, and only a limited number of pentapeptides (namely 107) identify SARS-CoV-2 spike gp as nonself when compared with the human proteome, and (2) the small phenetic difference practically disappears at the genetic level. Indeed, almost all of the 107 pentadecameric nucleotide sequences coding for the pentapeptides unique to SARS-CoV-2 spike gp are present in human nucleic acids too. Conclusion The data are of immunological significance for defining the issue of the viral versus human specificity and likely explain the fact that false positives can occur in serological and PCR tests for SARS-CoV-2 detection., Competing Interests: Conflicts of Interest None declared., (The Indian Association of Laboratory Physicians. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)
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- 2022
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30. SARS-CoV-2-Induced Immunosuppression: A Molecular Mimicry Syndrome.
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Kanduc D
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Background Contrary to immunological expectations, decay of adaptive responses against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) characterizes recovered patients compared with patients who had a severe disease course or died following SARS-CoV-2 infection. This raises the question of the causes of the virus-induced immune immunosuppression. Searching for molecular link(s) between SARS-CoV-2 immunization and the decay of the adaptive immune responses, SARS-CoV-2 proteome was analyzed for molecular mimicry with human proteins related to immunodeficiency. The aim was to verify the possibility of cross-reactions capable of destroying the adaptive immune response triggered by SARS-CoV-2. Materials and Methods Human immunodeficiency-related proteins were collected from UniProt database and analyzed for sharing of minimal immune determinants with the SARS-CoV-2 proteome. Results Molecular mimicry and consequent potential cross-reactivity exist between SARS-CoV-2 proteome and human immunoregulatory proteins such as nuclear factor kappa B (NFKB), and variable diversity joining V(D)J recombination-activating gene (RAG). Conclusion The data (1) support molecular mimicry and the associated potential cross-reactivity as a mechanism that can underlie self-reactivity against proteins involved in B- and T-cells activation/development, and (2) suggest that the extent of the immunosuppression is dictated by the extent of the immune responses themselves. The higher the titer of the immune responses triggered by SARS-CoV-2 immunization, the more severe can be the cross-reactions against the human immunodeficiency-related proteins, the more severe the immunosuppression. Hence, SARS-CoV-2-induced immunosuppression can be defined as a molecular mimicry syndrome. Clinically, the data imply that booster doses of SARS-CoV-2 vaccines may have opposite results to those expected., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)
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- 2022
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31. Nucleotide Sequence Sharing between the Human Genome and Primers for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Detection.
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Kanduc D
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This study shows that oligonucleotide sequences are shared between the human genome and primers that have been proposed/used for SARS-CoV-2 detection by polymerase chain reaction (PCR). The high level of sharing (namely, up to 19mer with a maximum number of gaps equal to 2) might bear implications for the diagnostic validity of SARS-CoV-2 detection by PCR., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)
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- 2022
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32. Retraction notice to "Why are we vaccinating children against COVID-19?" [Toxicol. Rep. 8 (2021) 1665-1684].
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Kostoff RN, Calina D, Kanduc D, Briggs MB, Vlachoyiannopoulos P, Svistunov AA, and Tsatsakis A
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[This retracts the article DOI: 10.1016/j.toxrep.2021.08.010.]., (© 2022 The Authors.)
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33. From Genetics to Epigenetics: Top 4 Aspects for Improved SARS-CoV-2 Vaccine Designs as Paradigmatic Examples.
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Kanduc D
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This literature review described the genetic and biochemical factors that may have been overlooked in the formulation of vaccines and that most likely underlie possible issues with mass vaccination., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)
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- 2021
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34. COVID-19: adrenal response and molecular mimicry.
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Churilov LP, Kanduc D, and Ryabkova VA
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- Adrenal Glands immunology, Adrenal Glands virology, Humans, Inflammation Mediators immunology, Receptors, Angiotensin immunology, Receptors, Corticotropin immunology, SARS-CoV-2 physiology, Post-Acute COVID-19 Syndrome, Adrenal Insufficiency etiology, Adrenal Insufficiency immunology, Adrenal Insufficiency virology, Autoimmunity immunology, COVID-19 complications, COVID-19 immunology, Molecular Mimicry immunology
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- 2021
35. From Anti-SARS-CoV-2 Immune Response to the Cytokine Storm via Molecular Mimicry.
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Kanduc D
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The aim of this study was to investigate the role of molecular mimicry in the cytokine storms associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human proteins endowed with anti-inflammatory activity were assembled and analyzed for peptide sharing with the SARS-CoV-2 spike glycoprotein (gp) using public databases. It was found that the SARS-CoV-2 spike gp shares numerous pentapeptides with anti-inflammatory proteins that, when altered, can lead to cytokine storms characterized by diverse disorders such as systemic multiorgan hyperinflammation, macrophage activation syndrome, ferritinemia, endothelial dysfunction, and acute respiratory syndrome. Immunologically, many shared peptides are part of experimentally validated epitopes and are also present in pathogens to which individuals may have been exposed following infections or vaccinal routes and of which the immune system has stored memory. Such an immunologic imprint might trigger powerful anamnestic secondary cross-reactive responses, thus explaining the raging of the cytokine storm that can occur following exposure to SARS-CoV-2. In conclusion, the results support molecular mimicry and the consequent cross-reactivity as a potential mechanism in SARS-CoV-2-induced cytokine storms, and highlight the role of immunological imprinting in determining high-affinity, high-avidity, autoimmune cross-reactions as a pathogenic sequela associated with anti-SARS-CoV-2 vaccines.
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- 2021
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36. From Anti-Severe Acute Respiratory Syndrome Coronavirus 2 Immune Response to Cancer Onset via Molecular Mimicry and Cross-Reactivity.
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Kanduc D
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Background and Objectives Whether exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may predispose to the risk of cancer in individuals with no prior cancers is a crucial question that remains unclear. To confirm/refute possible relationships between exposure to the virus and ex novo insurgence of tumors, this study analyzed molecular mimicry and the related cross-reactive potential between SARS-CoV-2 spike glycoprotein (gp) antigen and human tumor-suppressor proteins. Materials and Methods Tumor-associated proteins were retrieved from UniProt database and analyzed for pentapeptide sharing with SARS-CoV-2 spike gp by using publicly available databases. Results An impressively high level of molecular mimicry exists between SARS-CoV-2 spike gp and tumor-associated proteins. Numerically, 294 tumor-suppressor proteins share 308 pentapeptides with the viral antigen. Crucially, the shared peptides have a relevant immunologic potential by repeatedly occurring in experimentally validated epitopes. Such immunologic potential is of further relevancy in that most of the shared peptides are also present in infectious pathogens to which, in general, human population has already been exposed, thus indicating the possibility of immunologic imprint phenomena. Conclusion This article described a vast peptide overlap between SARS-CoV-2 spike gp and tumor-suppressor proteins, and supports autoimmune cross-reactivity as a potential mechanism underlying prospective cancer insurgence following exposure to SARS-CoV-2. Clinically, the findings call for close surveillance of tumor sequelae that possibly could result from the current coronavirus pandemic., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)
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- 2021
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37. Human Codon Usage: The Genetic Basis of Pathogen Latency.
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Kanduc D
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Infectious diseases pose two main compelling issues. First, the identification of the molecular factors that allow chronic infections, that is, the often completely asymptomatic coexistence of infectious agents with the human host. Second, the definition of the mechanisms that allow the switch from pathogen dormancy to pathologic (re)activation. Furthering previous studies, the present study (1) analyzed the frequency of occurrence of synonymous codons in coding DNA, that is, codon usage, as a genetic tool that rules protein expression; (2) described how human codon usage can inhibit protein expression of infectious agents during latency, so that pathogen genes the codon usage of which does not conform to the human codon usage cannot be translated; and (3) framed human codon usage among the front-line instruments of the innate immunity against infections. In parallel, it was shown that, while genetics can account for the molecular basis of pathogen latency, the changes of the quantitative relationship between codon frequencies and isoaccepting tRNAs during cell proliferation offer a biochemical mechanism that explains the pathogen switching to (re)activation. Immunologically, this study warns that using codon optimization methodologies can (re)activate, potentiate, and immortalize otherwise quiescent, asymptomatic pathogens, thus leading to uncontrollable pandemics., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)
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- 2021
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38. Thromboses and Hemostasis Disorders Associated with COVID-19: The Possible Causal Role of Cross-Reactivity and Immunological Imprinting.
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Kanduc D
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By examining the issue of the thromboses and hemostasis disorders associated with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) through the lens of cross-reactivity, it was found that 60 pentapeptides are shared by SARS-CoV-2 spike glycoprotein (gp) and human proteins that- when altered, mutated, deficient or, however, improperly functioning- cause vascular diseases, thromboembolic complications, venous thrombosis, thrombocytopenia, coagulopathies, and bleeding, inter alia. The peptide commonality has a relevant immunological potential as almost all of the shared sequences are present in experimentally validated SARS-CoV-2 spike gp-derived epitopes, thus supporting the possibility of cross-reactions between the viral gp and the thromboses-related human proteins. Moreover, many of the shared peptide sequences are also present in pathogens to which individuals have previously been exposed following natural infection or vaccinal routes, and of which the immune system has stored imprint. Such an immunological memory might rapidly trigger anamnestic secondary cross-reactive responses of extreme affinity and avidity, in this way explaining the thromboembolic adverse events that can associate with SARS-CoV-2 infection or active immunization., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)
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- 2021
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39. Lack of Molecular Mimicry between Nonhuman Primates and Infectious Pathogens: The Possible Genetic Bases.
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Kanduc D
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Recently, it was found that proteomes from poliovirus, measles virus, dengue virus, and severe acute respiratory syndrome-related Coronavirus 2 (SARS-CoV-2) have high molecular mimicry at the heptapeptide level with the human proteome, while heptapeptide commonality is minimal or absent with proteomes from nonhuman primates, that is, gorilla, chimpanzee, and rhesus macaque. To acquire more data on the issue, analyses here have been expanded to Ebola virus, Francisella tularensis , human immunodeficiency virus-1 (HIV-1), Toxoplasma gondii , Variola virus, and Yersinia pestis . Results confirm that heptapeptide overlap is high between pathogens and Homo sapiens , but not between pathogens and primates. Data are discussed in light of the possible genetic bases that differently model primate phenomes, thus possibly underlying the zero/low level of molecular mimicry between infectious agents and primates. Notably, this study might help address preclinical vaccine tests that currently utilize primates as animal models, since autoimmune cross-reactions and the consequent adverse events cannot occur in absentia of shared sequences., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)
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- 2021
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40. Sjögren's Syndrome Associated with Chikungunya Infection: A Case Report.
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de Carvalho JF, Kanduc D, da Silva FF, Tanay A, Lucchese A, and Shoenfeld Y
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Chikungunya virus (CHIKV) infection is caused by an arbovirus prevalent in various parts of the world. The virus can induce autoantibodies and rheumatic diseases, such as rheumatoid arthritis and spondylarthritis. However, until now, no case of Sjögren syndrome (SS) was described associated with CHIKV. In this article, we describe a 49-year-old female with polyarthralgia and a temporary rash on her trunk and arms. Her physical examination showed polyarthritis of her ankles and wrists. Serologies for CHIKV were interpreted as positive with IgM 6.5 (normal range < 0.8) and negative for IgG. Antinuclear antibodies were positive at a titer of 1:640 as well as anti-Ro/SS-A. The diagnosis of subacute CHIKV infection was determined. The Schirmer test, Rose Bengal, and salivary scintigraphy were positive and the diagnosis of SS was confirmed. She was treated with hydroxychloroquine, methotrexate, and a single dose of betamethasone depot. This is the first report on CHIKV associated with SS. Sequence analysis of the CHIKV proteome versus SS autoantigens showed an extensive peptide sharing between the virus and numerous SS autoantigens, thus supporting the hypothesis that autoimmune cross-reactivity might causally link CHIKV to SS.
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- 2021
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41. Common contributing factors to COVID-19 and inflammatory bowel disease.
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Kostoff RN, Briggs MB, Kanduc D, Shores DR, Kovatsi L, Vardavas AI, and Porter AL
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The devastating complications of coronavirus disease 2019 (COVID-19) result from an individual's dysfunctional immune response following the initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Multiple toxic stressors and behaviors contribute to underlying immune system dysfunction. SARS-CoV-2 exploits the dysfunctional immune system to trigger a chain of events ultimately leading to COVID-19. We have previously identified many contributing factors (CFs) (representing toxic exposure, lifestyle factors and psychosocial stressors) common to myriad chronic diseases. We hypothesized significant overlap between CFs associated with COVID-19 and inflammatory bowel disease (IBD), because of the strong role immune dysfunction plays in each disease. A streamlined dot-product approach was used to identify potential CFs to COVID-19 and IBD. Of the fifty CFs to COVID-19 that were validated for demonstration purposes, approximately half had direct impact on COVID-19 (the CF and COVID-19 were mentioned in the same record; i.e., CF---→COVID-19), and the other half had indirect impact. The nascent character of the COVID-19 core literature (∼ one year old) did not allow sufficient time for the direct impacts of many CFs on COVID-19 to be identified. Therefore, an immune system dysfunction (ID) literature directly related to the COVID-19 core literature was used to augment the COVID-19 core literature and provide the remaining CFs that impacted COVID-19 indirectly (i.e., CF---→immune system dysfunction---→COVID-19). Approximately 13000 potential CFs for myriad diseases (obtained from government and university toxic substance lists) served as the starting point for the dot-product identification process. These phrases were intersected (dot-product) with phrases extracted from a PubMed-derived IBD core literature, a nascent COVID-19 core literature, and the COVID-19-related immune system dysfunction (ID) core literature to identify common ID/COVID-19 and IBD CFs. Approximately 3000 potential CFs common to both ID and IBD, almost 2300 potential CFs common to ID and COVID-19, and over 1900 potential CFs common to IBD and COVID-19 were identified. As proof of concept, we validated fifty of these ∼3000 overlapping ID/IBD candidate CFs with biologic plausibility. We further validated 24 of the fifty as common CFs in the IBD and nascent COVID-19 core literatures. This significant finding demonstrated that the CFs indirectly related to COVID-19 -- identified with use of the immune system dysfunction literature -- are strong candidates to emerge eventually as CFs directly related to COVID-19. As discussed in the main text, many more CFs common to all these core literatures could be identified and validated. ID and IBD share many common risk/contributing factors, including behaviors and toxic exposures that impair immune function. A key component to immune system health is removal of those factors that contribute to immune system dysfunction in the first place. This requires a paradigm shift from traditional Western medicine, which often focuses on treatment, rather than prevention., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)
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- 2021
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42. Erratum to "Why are we vaccinating children against COVID-19?" [Toxicol. Rep. 8C (2021) 1665-1684 / 1193].
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Kostoff RN, Calina D, Kanduc D, Briggs MB, Vlachoyiannopoulos P, Svistunov AA, and Tsatsakis A
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[This corrects the article DOI: 10.1016/j.toxrep.2021.08.010.]., (© 2021 The Author(s).)
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- 2021
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43. Why are we vaccinating children against COVID-19?
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Kostoff RN, Calina D, Kanduc D, Briggs MB, Vlachoyiannopoulos P, Svistunov AA, and Tsatsakis A
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This article examines issues related to COVID-19 inoculations for children. The bulk of the official COVID-19-attributed deaths per capita occur in the elderly with high comorbidities, and the COVID-19 attributed deaths per capita are negligible in children. The bulk of the normalized post-inoculation deaths also occur in the elderly with high comorbidities, while the normalized post-inoculation deaths are small, but not negligible, in children. Clinical trials for these inoculations were very short-term (a few months), had samples not representative of the total population, and for adolescents/children, had poor predictive power because of their small size. Further, the clinical trials did not address changes in biomarkers that could serve as early warning indicators of elevated predisposition to serious diseases. Most importantly, the clinical trials did not address long-term effects that, if serious, would be borne by children/adolescents for potentially decades. A novel best-case scenario cost-benefit analysis showed very conservatively that there are five times the number of deaths attributable to each inoculation vs those attributable to COVID-19 in the most vulnerable 65+ demographic. The risk of death from COVID-19 decreases drastically as age decreases, and the longer-term effects of the inoculations on lower age groups will increase their risk-benefit ratio, perhaps substantially., Competing Interests: The authors declare that they have no competing interests, (© 2021 The Author(s).)
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- 2021
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44. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): Codon Usage and Replicative Fitness.
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Kanduc D
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) codon usage, as shown by the polyprotein coding sequence, shows better translation potential in the human host when compared with human coronavirus OC43 (HCoV-OC43) codon usage. Such translational advantage might facilitate SARS-CoV-2 replication, immunogenicity, and pathogenicity, thus also accounting for the less harmful character of HCoV-OC43 infection., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)
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- 2020
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45. From Anti-EBV Immune Responses to the EBV Diseasome via Cross-reactivity.
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Kanduc D and Shoenfeld Y
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Sequence analyses highlight a massive peptide sharing between immunoreactive Epstein-Barr virus (EBV) epitopes and human proteins that-when mutated, deficient or improperly functioning-associate with tumorigenesis, diabetes, lupus, multiple sclerosis, rheumatoid arthritis, and immunodeficiencies, among others. Peptide commonality appears to be the molecular platform capable of linking EBV infection to the vast EBV-associated diseasome via cross-reactivity and questions the hypothesis of the "negative selection" of self-reactive lymphocytes. Of utmost importance, this study warns that using entire antigens in anti-EBV immunotherapies can associate with autoimmune manifestations and further supports the concept of peptide uniqueness for designing safe and effective anti-EBV immunotherapies., Competing Interests: Conflict of Interest D.K. declares no conflicts. Y.S. is a medical consultant in vaccine compensation court, United States., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)
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- 2020
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46. Medical, Genomic, and Evolutionary Aspects of the Peptide Sharing between Pathogens, Primates, and Humans.
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Kanduc D and Shoenfeld Y
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Comparing mammalian proteomes for molecular mimicry with infectious pathogens highlights the highest levels of heptapeptide sharing between pathogens and human, murine, and rat proteomes, while the peptide sharing level is minimal (or absent) with proteomes from nonhuman primates such as gorilla, chimpanzee, and rhesus macaque. From the medical point of view, the data might be useful to clinicians and vaccinologists to develop and evaluate immunomodulatory and immunotherapeutic approaches. As a matter of fact, primates seem to be unreliable animal models for revealing potential autoimmune events in preclinical testing of immunotherapies. In terms of genomics, the scarce or absent peptide sharing between pathogens and primates versus the massive peptide sharing existing between pathogens and humans lets foresee mechanisms of pathogen sequence insertion/deletion/alteration that have differently operated in mammals over evolutionary timescales. Why and how the human genome has been colonized by pathogen sequences and why and how primates escaped such a colonization appears to be the new scientific challenge in our efforts to understand not only the origin of Homo sapiens but also his autoimmune diseasome., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)
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- 2020
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47. From Anti-SARS-CoV-2 Immune Responses to COVID-19 via Molecular Mimicry.
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Kanduc D
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Aim: To define the autoimmune potential of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection., Methods: Experimentally validated epitopes cataloged at the Immune Epitope DataBase (IEDB) and present in SARS-CoV-2 were analyzed for peptide sharing with the human proteome., Results: Immunoreactive epitopes present in SARS-CoV-2 were mostly composed of peptide sequences present in human proteins that-when altered, mutated, deficient or, however, improperly functioning-may associate with a wide range of disorders, from respiratory distress to multiple organ failure., Conclusions: This study represents a starting point or hint for future scientific-clinical investigations and suggests a range of possible protein targets of autoimmunity in SARS-CoV-2 infection. From an experimental perspective, the results warrant the testing of patients' sera for autoantibodies against these protein targets. Clinically, the results warrant a stringent surveillance on the future pathologic sequelae of the current SARS-CoV-2 pandemic.
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- 2020
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48. Vaccine- and natural infection-induced mechanisms that could modulate vaccine safety.
- Author
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Kostoff RN, Kanduc D, Porter AL, Shoenfeld Y, Calina D, Briggs MB, Spandidos DA, and Tsatsakis A
- Abstract
A degraded/dysfunctional immune system appears to be the main determinant of serious/fatal reaction to viral infection (for COVID-19, SARS, and influenza alike). There are four major approaches being employed or considered presently to augment or strengthen the immune system, in order to reduce adverse effects of viral exposure. The three approaches that are focused mainly on augmenting the immune system are based on the concept that pandemics/outbreaks can be controlled/prevented while maintaining the immune-degrading lifestyles followed by much of the global population. The fourth approach is based on identifying and introducing measures aimed at strengthening the immune system intrinsically in order to minimize future pandemics/outbreaks. Specifically, the four measures are: 1) restricting exposure to virus; 2) providing reactive/tactical treatments to reduce viral load; 3) developing vaccines to prevent, or at least attenuate, the infection; 4) strengthening the immune system intrinsically, by a) identifying those factors that contribute to degrading the immune system, then eliminating/reducing them as comprehensively, thoroughly, and rapidly as possible, and b) replacing the eliminated factors with immune-strengthening factors. This paper focuses on vaccine safety. A future COVID-19 vaccine appears to be the treatment of choice at the national/international level. Vaccine development has been accelerated to achieve this goal in the relatively near-term, and questions have arisen whether vaccine safety has been/is being/will be compromised in pursuit of a shortened vaccine development time. There are myriad mechanisms related to vaccine-induced, and natural infection-induced, infections that could adversely impact vaccine effectiveness and safety. This paper summarizes many of those mechanisms., Competing Interests: The authors report no declarations of interest., (© 2020 The Author(s).)
- Published
- 2020
- Full Text
- View/download PDF
49. Proteome-Wide Epstein-BarrVirus Analysis of Peptide Sharing with Human Systemic Lupus Erythematosus Autoantigens.
- Author
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Kanduc D
- Subjects
- Complement C4 immunology, Cross Reactions immunology, Databases, Factual, Herpesvirus 4, Human immunology, Humans, Interleukin-10 immunology, Autoantigens immunology, Epstein-Barr Virus Infections immunology, Lupus Erythematosus, Systemic immunology, Peptides immunology, Proteome
- Abstract
Background: Although cross-reactions between Epstein-Barr virus (EBV) and human systemic lupus erythematosus (SLE) autoantigens occur, a complete analysis of the potential EBV peptide cross-reactome has not been performed., Objectives: To analyze the whole EBV proteome searching for peptides common to SLE-related proteins and endowed with an immunological potential., Methods: Fifty-one SLE-related proteins were analyzed for hexapeptide sharing with EBV proteome using publicly available databases., Results: An extremely high number of hexapeptides are shared between 34 human SLE autoantigens and EBV proteins. The peptide sharing mostly occurs with complement components C4 and Interleukin-10 (IL-10)., Conclusions: This study thoroughly describes the EBV vs. SLE autoantigens peptide overlap and powerfully supports cross-reactivity as a major mechanism in EBV-associated SLE etiopathogenesis.
- Published
- 2019
50. EBV-Associated Cancer and Autoimmunity: Searching for Therapies.
- Author
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Capone G, Fasano C, Lucchese G, Calabrò M, and Kanduc D
- Abstract
Epstein-Barr virus (EBV) infects B-, T-, and NK cells and has been associated not only with a wide range of lymphoid malignancies but also with autoimmune diseases such as lupus erythematosus, rheumatoid arthritis and, in particular, multiple sclerosis. Hence, effective immunotherapeutic approaches to eradicate EBV infection might overthrow cancer and autoimmunity incidence. However, currently no effective anti-EBV immunotherapy is available. Here we use the concept that protein immunogenicity is allocated in rare peptide sequences and search the Epstein-Barr nuclear antigen 1 (EBNA1) sequence for peptides unique to the viral protein and absent in the human host. We report on a set of unique EBV EBNA1 peptides that might be used in designing peptide-based therapies able to specifically hitting the virus or neutralizing pathogenic autoantibodies.
- Published
- 2015
- Full Text
- View/download PDF
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