Anti Transglutaminase Antibodies Cause Ataxia in Mice
Publication Date
March 15, 2010
Journal
PLOS ONE
Authors
Sabrina Boscolo, Andrea Lorenzon, Daniele Sblattero, Fiorella Florian, et al
Volume
5
Issue
3
Pages
e9698
DOI
https://dx.plos.org/10.1371/journal.pone.0009698
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0009698
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/20300628
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2837746
Europe PMC
http://europepmc.org/abstract/MED/20300628
Web of Science
000275621000015
Scopus
77956185452
Mendeley
http://www.mendeley.com/research/anti-transglutaminase-antibodies-cause-ataxia-mice
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Mendeley | Further Information

{"title"=>"Anti transglutaminase antibodies cause ataxia in mice", "type"=>"journal", "authors"=>[{"first_name"=>"Sabrina", "last_name"=>"Boscolo", "scopus_author_id"=>"21933381800"}, {"first_name"=>"Andrea", "last_name"=>"Lorenzon", "scopus_author_id"=>"21934569400"}, {"first_name"=>"Daniele", "last_name"=>"Sblattero", "scopus_author_id"=>"6603945012"}, {"first_name"=>"Fiorella", "last_name"=>"Florian", "scopus_author_id"=>"6602729836"}, {"first_name"=>"Marco", "last_name"=>"Stebel", "scopus_author_id"=>"6603133430"}, {"first_name"=>"Roberto", "last_name"=>"Marzari", "scopus_author_id"=>"6701364200"}, {"first_name"=>"Tarcisio", "last_name"=>"Not", "scopus_author_id"=>"7004011540"}, {"first_name"=>"Daniel", "last_name"=>"Aeschlimann", "scopus_author_id"=>"7003942503"}, {"first_name"=>"Alessandro", "last_name"=>"Ventura", "scopus_author_id"=>"35447347000"}, {"first_name"=>"Marios", "last_name"=>"Hadjivassiliou", "scopus_author_id"=>"35602428700"}, {"first_name"=>"Enrico", "last_name"=>"Tongiorgi", "scopus_author_id"=>"6603834718"}], "year"=>2010, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"77956185452", "pui"=>"368277901", "doi"=>"10.1371/journal.pone.0009698", "pmid"=>"20300628", "scopus"=>"2-s2.0-77956185452", "issn"=>"19326203", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"8b7b61f8-0bf1-3b98-99d6-dab2c56d45eb", "abstract"=>"BACKGROUND: Celiac disease (CD) is an autoimmune gastrointestinal disorder characterized by the presence of anti-transglutaminase 2 (TG2) and anti-gliadin antibodies. Amongst the neurological dysfunctions associated with CD, ataxia represents the most common one. METHODS: We analyzed by immunohistochemistry, the anti-neural reactivity of the serum from 20 CD patients. To determine the role of anti-TG2 antibodies in ataxia, two anti-TG2 single chain variable fragments (scFv), isolated from a phage-display IgA antibody library, were characterized by immunohistochemistry and ELISA, and injected in mice to study their effects on motor coordination. We found that 75% of the CD patient population without evidence of neurological involvement, has circulating anti-neural IgA and/or IgG antibodies. Two anti-TG2 scFvs, cloned from one CD patient, stained blood vessels but only one reacted with neurons. This anti-TG2 antibody showed cross reactivity with the transglutaminase isozymes TG3 and TG6. Intraventricular injection of the anti-TG2 or the anti-TG2/3/6 cross-reactive scFv provoked transient, equally intensive ataxia in mice. CONCLUSION: The serum from CD patients contains anti-TG2, TG3 and TG6 antibodies that may potentially cause ataxia.", "link"=>"http://www.mendeley.com/research/anti-transglutaminase-antibodies-cause-ataxia-mice", "reader_count"=>45, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>5, "Librarian"=>1, "Researcher"=>8, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>9, "Student > Postgraduate"=>1, "Student > Master"=>4, "Other"=>3, "Student > Bachelor"=>6, "Lecturer"=>2, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>5, "Librarian"=>1, "Researcher"=>8, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>9, "Student > Postgraduate"=>1, "Student > Master"=>4, "Other"=>3, "Student > Bachelor"=>6, "Lecturer"=>2, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>3, "Nursing and Health Professions"=>1, "Agricultural and Biological Sciences"=>21, "Medicine and Dentistry"=>8, "Neuroscience"=>2, "Sports and Recreations"=>2, "Business, Management and Accounting"=>1, "Chemistry"=>3, "Psychology"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>8}, "Neuroscience"=>{"Neuroscience"=>2}, "Chemistry"=>{"Chemistry"=>3}, "Sports and Recreations"=>{"Sports and Recreations"=>2}, "Psychology"=>{"Psychology"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>21}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>1}, "Environmental Science"=>{"Environmental Science"=>1}}, "reader_count_by_country"=>{"United States"=>1, "Finland"=>1, "Italy"=>1, "United Kingdom"=>1, "Germany"=>1}, "group_count"=>2}

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Scopus | Further Information

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  • {"files"=>["https://ndownloader.figshare.com/files/858602"], "description"=>"<p>The class1 anti-TG2 scFv strongly labeled rat esophagus (A), with the reticular staining pattern typical for TG2, the tunica adventitia of brain and cerebellum vessels (B) and to a lesser extent brain and cerebellum capillaries (C) but did not recognize brain neurons (D, E). In contrast, the class2 anti-TG2 scFv showed a very faint and diffuse labeling on esophagus sections (F) but strongly labeled the tunica media of brain and cerebellum vessels (G), recognized brain and cerebellar microvessels (H) and also neurons including Purkinje cells (I) and brainstem neurons (J). The monoclonal anti-TG2 antibody CUB7402 reacted on rat tissues with a pattern that is reminiscent of the staining pattern of class1 scFv (K–O). Bac1, a non relevant scFv used as negative control, showed no labeling on rat esophagus (P) brain vessels (Q, R) or neurons (S, T). Calibration bars = 10 µm for C, H, M, R 40 µm for B, G, L, Q and 20 µm for the others. To confirm their specificity, the scFvs were also tested in ELISA on different brain homogenates and on human recombinant TG2. As expected, both class1 and class2 scFvs recognized TG2. However, only the class2 scFv reacted with an epitope in human and rat brain extracts. This epitope was present in brain lysates from wt or TG2<sup>−/−</sup> mice suggesting that it is not TG2. Bac1 was negative on each substrate used for coating (U).</p>", "links"=>[], "tags"=>["staining", "patterns", "cd", "derived", "class1", "class2", "iga", "scfvs", "tg2", "esophagus"], "article_id"=>529040, "categories"=>["Immunology", "Biotechnology", "Neuroscience"], "users"=>["Sabrina Boscolo", "Andrea Lorenzon", "Daniele Sblattero", "Fiorella Florian", "Marco Stebel", "Roberto Marzari", "Tarcisio Not", "Daniel Aeschlimann", "Alessandro Ventura", "Marios Hadjivassiliou", "Enrico Tongiorgi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0009698.g003", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Distinct_staining_patterns_of_CD_patient_derived_class1_and_class2_IgA_scFvs_to_TG2_on_rat_esophagus_and_brain_sections_/529040", "title"=>"Distinct staining patterns of CD patient derived class1 and class2 IgA scFvs to TG2 on rat esophagus and brain sections.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-03-15 02:30:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/858757"], "description"=>"<p>Anti TG2 scFvs were tested in ELISA on human recombinant TG3 or TG6 as an antigen to determine whether they recognize an epitope that is shared between different TG isozymes. Class2 scFv is reactive with both TG3 and TG6 (P<0,001 *** one way Anova) in contrast to class1 which reacts exclusively with TG2.</p>", "links"=>[], "tags"=>["reactivity", "class2", "class1", "scfv"], "article_id"=>529205, "categories"=>["Immunology", "Biotechnology", "Neuroscience"], "users"=>["Sabrina Boscolo", "Andrea Lorenzon", "Daniele Sblattero", "Fiorella Florian", "Marco Stebel", "Roberto Marzari", "Tarcisio Not", "Daniel Aeschlimann", "Alessandro Ventura", "Marios Hadjivassiliou", "Enrico Tongiorgi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0009698.g004", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cross_reactivity_of_class2_but_not_class1_scFv_with_different_TGases_/529205", "title"=>"Cross reactivity of class2 but not class1 scFv with different TGases.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-03-15 02:33:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/859045"], "description"=>"<p>Biotinylated scFvs were revealed 3 h after injection by incubating FITC-conjugated streptavidin on brain sections. Brain vessels were stained with anti-von Willebrand Factor (vWF) followed by TRITC conjugated anti-rabbit. Confocal images on sections from mice injected with biotinylated class1 (A) and class2 (B) showed the localization of these antibodies on small brain vessels structures in some cases colocalizing with vWF (class2 B). No presence of bac1 (C) scFv was detected on brain vessels. Calibration bar = 5 µm.</p>", "links"=>[], "tags"=>["anti-tg2", "scfvs", "intraventricular"], "article_id"=>529492, "categories"=>["Immunology", "Biotechnology", "Neuroscience"], "users"=>["Sabrina Boscolo", "Andrea Lorenzon", "Daniele Sblattero", "Fiorella Florian", "Marco Stebel", "Roberto Marzari", "Tarcisio Not", "Daniel Aeschlimann", "Alessandro Ventura", "Marios Hadjivassiliou", "Enrico Tongiorgi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0009698.g006", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Localization_of_anti_TG2_scFvs_after_intraventricular_delivery_on_small_brain_vessels_/529492", "title"=>"Localization of anti-TG2 scFvs after intraventricular delivery on small brain vessels.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-03-15 02:38:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/858437"], "description"=>"<p>Immunohistochemical staining on rat esophagus and brainstem neurons with CD patient serum before (A, C, E) and after depletion of anti-TG2 autoantibodies (B, D, F). Both IgAs (A) and IgGs (not shown) labeled rat esophagus in a pattern reminiscent of that of TG2 distribution in the tissue. The patient's serum also labeled rat neurons in the brainstem (C, IgAs; E, IgGs) with a strong perinuclear staining. After adsorption on recombinant human TG2, no IgA binding to rat esophagus sections could be detected (B). On rat neurons, TG2 adsorption eliminated the IgA reactivity both at the cytoplasmic and nuclear level (D, arrowheads) while the IgG staining was reduced at the cytoplasmic level but remained almost unaltered in the perinuclear area (F, arrowheads). Calibration bars = 20 µm.</p>", "links"=>[], "tags"=>["cd", "serum", "antibodies", "recombinant", "tg2", "neuronal"], "article_id"=>528880, "categories"=>["Immunology", "Biotechnology", "Neuroscience"], "users"=>["Sabrina Boscolo", "Andrea Lorenzon", "Daniele Sblattero", "Fiorella Florian", "Marco Stebel", "Roberto Marzari", "Tarcisio Not", "Daniel Aeschlimann", "Alessandro Ventura", "Marios Hadjivassiliou", "Enrico Tongiorgi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0009698.g002", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Adsorption_of_CD_serum_antibodies_on_recombinant_human_TG2_reduces_substantially_the_recognition_of_neuronal_epitopes_/528880", "title"=>"Adsorption of CD serum antibodies on recombinant human TG2 reduces substantially the recognition of neuronal epitopes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-03-15 02:28:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/858859"], "description"=>"<p>The effective delivery of the scFvs after injection, was confirmed on transverse brain sections by detection of the injected biotin conjugated scFvs with streptavidin conjugated horseradish peroxidase. Sections of untreated mice incubated with streptavidin-peroxidase alone showed no discrete labeling (A) whereas sections from mice injected with biotinylated class1 (B), class2 (C) or bac1 (D) scFv clearly demonstrated the presence of these in the lateral ventricles of mice 3 h after injection (asterisks) and in the brain parenchyma even at considerable distance from the ventricles (cerebellum, long arrows; collicoli, short arrows). Mice treated with monoclonal antibodies were tested at 5 h, after antibody injection for gait imbalance with footprint analysis. The R-L overlap clearly demonstrated that the control scFv bac1 had no effect on mice gait (E, arrows, front paws colored with red, back paws colored with blue), on the contrary with both class1 and class2 there was no overlap between left or righ front and back paws (F–G, arrowheads). In particular, four step parameters have been recorded, namely, stride length (H), front and hind-base width (I) and overlap between forepaw and hindpaw placement (J). Mice injected with anti-TG2 monoclonal antibody class1 exhibited a significant shorter forelimb stride length and a less marked hindlimb stride length (H) compared to mice treated with the negative control monoclonal antibody bac1. There was no significant difference between mice injected with class1 or bac1 for the hind and front-base width (I) while mice treated with class1 displayed a greater distance between fore/hindpaw overlap compared to that produced by negative control injected mice (J). Mice injected with monoclonal antibody class2 showed indistinguishable forelimb and hindlimb stride length from those produced by negative control mice (H) a little decrease in the fore and hind-base width (I) while showed a significant different overlap measurement compared to the negative control mice (J). Bars represent the mean value of each measurement considered, n is the number of mice injected with the monoclonal antibodies. Error bars represent SE. <b>°°°</b> P = 0,002 one way ANOVA class 1 compared to bac1. <b>***</b> P<0,001 one way ANOVA class 1 compared to bac1 or class 2 compared to bac1.</p>", "links"=>[], "tags"=>["anti-tg2", "scfvs", "intraventricular", "footprint"], "article_id"=>529308, "categories"=>["Immunology", "Biotechnology", "Neuroscience"], "users"=>["Sabrina Boscolo", "Andrea Lorenzon", "Daniele Sblattero", "Fiorella Florian", "Marco Stebel", "Roberto Marzari", "Tarcisio Not", "Daniel Aeschlimann", "Alessandro Ventura", "Marios Hadjivassiliou", "Enrico Tongiorgi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0009698.g005", "stats"=>{"downloads"=>2, "page_views"=>27, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Localization_of_anti_TG2_scFvs_after_intraventricular_delivery_and_footprint_analysis_/529308", "title"=>"Localization of anti-TG2 scFvs after intraventricular delivery and footprint analysis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-03-15 02:35:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/426977", "https://ndownloader.figshare.com/files/427044", "https://ndownloader.figshare.com/files/427075", "https://ndownloader.figshare.com/files/427106", "https://ndownloader.figshare.com/files/427126"], "description"=>"<div><h3>Background</h3><p>Celiac disease (CD) is an autoimmune gastrointestinal disorder characterized by the presence of anti-transglutaminase 2 (TG2) and anti-gliadin antibodies. Amongst the neurological dysfunctions associated with CD, ataxia represents the most common one.</p><h3>Methods</h3><p>We analyzed by immunohistochemistry, the anti-neural reactivity of the serum from 20 CD patients. To determine the role of anti-TG2 antibodies in ataxia, two anti-TG2 single chain variable fragments (scFv), isolated from a phage-display IgA antibody library, were characterized by immunohistochemistry and ELISA, and injected in mice to study their effects on motor coordination. We found that 75% of the CD patient population without evidence of neurological involvement, has circulating anti-neural IgA and/or IgG antibodies. Two anti-TG2 scFvs, cloned from one CD patient, stained blood vessels but only one reacted with neurons. This anti-TG2 antibody showed cross reactivity with the transglutaminase isozymes TG3 and TG6. Intraventricular injection of the anti-TG2 or the anti-TG2/3/6 cross-reactive scFv provoked transient, equally intensive ataxia in mice.</p><h3>Conclusion</h3><p>The serum from CD patients contains anti-TG2, TG3 and TG6 antibodies that may potentially cause ataxia.</p></div>", "links"=>[], "tags"=>["anti", "transglutaminase", "antibodies", "ataxia", "mice"], "article_id"=>144275, "categories"=>["Immunology", "Biotechnology", "Neuroscience"], "users"=>["Sabrina Boscolo", "Andrea Lorenzon", "Daniele Sblattero", "Fiorella Florian", "Marco Stebel", "Roberto Marzari", "Tarcisio Not", "Daniel Aeschlimann", "Alessandro Ventura", "Marios Hadjivassiliou", "Enrico Tongiorgi"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0009698.s001", "https://dx.doi.org/10.1371/journal.pone.0009698.s002", "https://dx.doi.org/10.1371/journal.pone.0009698.s003", "https://dx.doi.org/10.1371/journal.pone.0009698.s004", "https://dx.doi.org/10.1371/journal.pone.0009698.s005"], "stats"=>{"downloads"=>6, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Anti_Transglutaminase_Antibodies_Cause_Ataxia_in_Mice/144275", "title"=>"Anti Transglutaminase Antibodies Cause Ataxia in Mice", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2010-03-15 01:11:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/858234"], "description"=>"<p>Immunohistochemical staining on rat Purkinje cells (left panels, arrow heads), deep cerebellar nuclei neurons (middle panels, arrow head) and brainstem reticular neurons (right panels) using either serum from a healthy donor (A–F) or from an untreated CD patient (G–L). No binding of serum IgAs (A–C) and IgGs (D–F) from healthy donors could be detected. In contrast, antibodies in sera of CD patient (positive for anti-TG2 IgA/IgG antibodies) stained the cytoplasm and the perinuclear zone of neurons from the three brain areas, both when detecting IgAs (G–I) or IgGs (J–L). Calibration bars = 20 µm.</p>", "links"=>[], "tags"=>["sections", "serum", "igas", "iggs", "cd"], "article_id"=>528676, "categories"=>["Immunology", "Biotechnology", "Neuroscience"], "users"=>["Sabrina Boscolo", "Andrea Lorenzon", "Daniele Sblattero", "Fiorella Florian", "Marco Stebel", "Roberto Marzari", "Tarcisio Not", "Daniel Aeschlimann", "Alessandro Ventura", "Marios Hadjivassiliou", "Enrico Tongiorgi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0009698.g001", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Reactivity_of_rat_brain_sections_with_serum_IgAs_and_IgGs_of_CD_patients_/528676", "title"=>"Reactivity of rat brain sections with serum IgAs and IgGs of CD patients.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-03-15 02:24:36"}

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  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"14", "full-text"=>"15", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
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  • {"unique-ip"=>"8", "full-text"=>"9", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
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  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
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  • {"unique-ip"=>"11", "full-text"=>"14", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"10", "full-text"=>"10", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
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Relative Metric

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