title: Induction of antitoxin responses in Clostridium-difficile-infected patients compared to healthy blood donors.
abstract: According to the literature Clostridium difficile antitoxins are present in up to 66% of humans. In a survey of ∼400 plasma samples from healthy blood donors we found that less than 6% were positive for anti-TcdA or anti-TcdB antitoxins. Using the same standard immunoassay protocol, we looked for IgG and IgA antitoxins in the blood and stool samples from 25 patients with C. difficile infection (CDI). Some patients with CDI had no antitoxin detected at all, while others had high levels of specific IgG- and IgA-antitoxins against both TcdA and TcdB in blood and IgA-anti-TcdA and -anti-TcdB antibodies in stool. Systemic responses to TcdB and mucosal responses to TcdA predominated. Among patients infected with the NAP1/027/BI strain, systemic IgG-anti-TcdB responses were particularly elevated. In contrast, patients infected with non-027 strains had more elevated mucosal IgA-anti-TcdA responses. Furthermore, high titer sera did not correlate with high neutralizing potential. We hypothesize that paradoxical killing of primed B-cells by antibody-mediated endosomal uptake of the Large Clostridial Toxins, TcdA and TcdB leads to clonal elimination of the fittest B-cells. If this hypothesis is confirmed, immune suppression rather than protective humoral immunity might be the consequence in some patients infected with toxigenic C. difficile.
authors.affiliation: Institut für Medizinische Mikrobiologie und Hygiene Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Hochhaus am Augustusplatz, Obere Zahlbacher Str. 67, D-55131 Mainz, Germany; Loyola University Stritch School of Medicine, Chicago, IL, USA.
authors.forename: Alice
authors.initials: A
authors.lastname: von Eichel-Streiber
authors.affiliation: Loyola University Stritch School of Medicine, Chicago, IL, USA.
authors.forename: Wonbeom
authors.initials: W
authors.lastname: Paik
authors.affiliation: Loyola University Stritch School of Medicine, Chicago, IL, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Knight
authors.affiliation: tgcBIOMICS GmbH, Franz-Kirsten-Str. 1, 55411 Bingen, Germany.
authors.forename: Karina
authors.initials: K
authors.lastname: Gisch
authors.affiliation: tgcBIOMICS GmbH, Franz-Kirsten-Str. 1, 55411 Bingen, Germany.
authors.forename: Karolina
authors.initials: K
authors.lastname: Nadjafi
authors.affiliation: tgcBIOMICS GmbH, Franz-Kirsten-Str. 1, 55411 Bingen, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Decker
authors.affiliation: Biomex GmbH, Siemensstrasse 38, D-69123 Heidelberg, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Bosnjak
authors.affiliation: Hines VA Hospital, Chicago, IL, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Cheknis
authors.affiliation: Loyola University Stritch School of Medicine, Chicago, IL, USA; Hines VA Hospital, Chicago, IL, USA.
authors.forename: Stuart
authors.initials: S
authors.lastname: Johnson
authors.affiliation: Institut für Medizinische Mikrobiologie und Hygiene Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Hochhaus am Augustusplatz, Obere Zahlbacher Str. 67, D-55131 Mainz, Germany; tgcBIOMICS GmbH, Franz-Kirsten-Str. 1, 55411 Bingen, Germany. Electronic address: chv.eichel@tgcbiomics.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: von Eichel-Streiber
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000907:Antibodies, Bacterial / Q000097:blood*; D000942:Antigens, Bacterial / Q000276:immunology; D001427:Bacterial Toxins / Q000276:immunology*; D001782:Blood Donors; D016022:Case-Control Studies; D016360:Clostridioides difficile / Q000235:genetics / Q000276:immunology*; D004761:Enterocolitis, Pseudomembranous / Q000097:blood / Q000276:immunology* / Q000401:mortality / Q000628:therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D058889:Molecular Typing; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001427:Bacterial Toxins
keywords: Anti-Toxin antibodies; Antigen presenting cell; C. difficile infection (CDI); Clostridium difficile; Recurrent CDI; Toxin A; Toxin B. clonal elimination