The role of the humoral immune response to Clostridium difficile toxins A and B in susceptibility to C. difficile infection: a case-control study.
Antibody levels to Clostridium difficile toxin A (TcdA), but not toxin B (TcdB), have been found to determine risk of C. difficile infection (CDI). Historically, TcdA was thought to be the key virulence factor; however the importance of TcdB in disease is now established. We re-evaluated the role of antibodies to TcdA and TcdB in determining patient susceptibility to CDI in two separate patient cohorts. In contrast to earlier studies, we find that CDI patients have lower pre-existing IgA titres to TcdB, but not TcdA, when compared to control patients. Our findings suggest that mucosal immunity to TcdB may be important in the early stages of infection and identifies a possible target for preventing CDI progression.
Pathogen Host Interaction Group, Division of Clinical Medicine, Brighton and Sussex Medical School, Medical School Research Building, University of Sussex, Brighton BN1 9PX, UK.
J
J
Islam
Pathogen Host Interaction Group, Division of Clinical Medicine, Brighton and Sussex Medical School, Medical School Research Building, University of Sussex, Brighton BN1 9PX, UK.
A L
AL
Taylor
Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
K
K
Rao
Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; Department of Microbiology & Immunology, University of Michigan, Ann Arbor, MI, USA.
G
G
Huffnagle
Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; Department of Microbiology & Immunology, University of Michigan, Ann Arbor, MI, USA.
V B
VB
Young
Department of Geriatric Medicine, Royal Sussex County Hospital, Brighton, UK.
C
C
Rajkumar
Pathogen Host Interaction Group, Division of Clinical Medicine, Brighton and Sussex Medical School, Medical School Research Building, University of Sussex, Brighton BN1 9PX, UK.
J
J
Cohen
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Albert-Ludwigs-Universität Freiburg, Germany.
P
P
Papatheodorou
Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; Department of Microbiology & Immunology, University of Michigan, Ann Arbor, MI, USA.
D M
DM
Aronoff
Pathogen Host Interaction Group, Division of Clinical Medicine, Brighton and Sussex Medical School, Medical School Research Building, University of Sussex, Brighton BN1 9PX, UK. Electronic address: m.j.llewelyn@bsms.ac.uk.
M J
MJ
Llewelyn
D036002:ADP Ribose Transferases / Q000276:immunology*; D000368:Aged; D000369:Aged, 80 and over; D000907:Antibodies, Bacterial / Q000032:analysis*; D000992:Antitoxins / Q000032:analysis*; D001426:Bacterial Proteins / Q000276:immunology*; D016022:Case-Control Studies; D003015:Clostridium Infections / Q000276:immunology* / Q000517:prevention & control*; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000032:analysis; D008297:Male; D008875:Middle Aged
D000907:Antibodies, Bacterial; D000992:Antitoxins; D001426:Bacterial Proteins; D007070:Immunoglobulin A; D036002:ADP Ribose Transferases; C410164:actin-specific ADP-ribosyltransferase, Clostridium
Case–control study; Clostridium difficile; Humoral immune response; Toxin A (TcdA); Toxin B (TcdB)