Skip to main content

Research Repository

Advanced Search

Protective antibodies against Clostridium difficile are present in intravenous immunoglobulin and are retained in humans following its administration

Negm, Ola H.; MacKenzie, B.; Hamed, M.R.; Ahmad, O.A.J.; Shone, Clifford C.; Humphreys, D.P.; Acharya, K. Ravi; Loscher, Christine E.; Marszalowska, Izabela; Lynch, Mark; Wilcox, Mark H.; Monaghan, Tanya M.

Authors

OLA NEGM ola.negm@nottingham.ac.uk
Teaching Associate and Problembased Learning Facilitator

B. MacKenzie

M.R. Hamed

O.A.J. Ahmad

Clifford C. Shone

D.P. Humphreys

K. Ravi Acharya

Christine E. Loscher

Izabela Marszalowska

Mark Lynch

Mark H. Wilcox

TANYA MONAGHAN Tanya.Monaghan@nottingham.ac.uk
Clinical Associate Professor in Luminal Gastroenterology



Abstract

The prevalence of serum antibodies against Clostridium difficile (CD) toxins A and B in healthy populations have prompted interest in evaluating the therapeutic activity of intravenous immunoglobulin (IVIg) in individuals experiencing severe or recurrent C. difficile infection (CDI). Despite some promising case reports, a definitive clinical role for IVIg in CDI remains unclear. Contradictory results may be attributed to a lack of consensus regarding optimal dose, timing of administration and patient selection as well as variability in specific antibody content between commercial preparations. The purpose of this study was to investigate retrospectively the efficacy of three commercial preparations of IVIg for treating severe or recurrent CDI. In subsequent mechanistic studies using protein microarray and toxin neutralization assays, all IVIg preparations were analysed for specific binding and neutralizing antibodies (NAb) to CD antigens in vitro and the presence of anti-toxin NAbs in vivo following IVIg infusion. A therapeutic response to IVIg was observed in 41% (10 of 17) of the CDI patients. Significant variability in multi-isotype specific antibodies to a 7-plex panel of CD antigens and toxin neutralization efficacies were observed between IVIg preparations and also in patient sera before and after IVIg administration. These results extend our current understanding of population immunity to CD and support the inclusion of surface layer proteins and binary toxin antigens in CD vaccines. Future strategies could enhance IVIg treatment response rates by using protein microarray to preselect donor plasma/serum with the highest levels of anti-CD antibodies and/or anti-toxin neutralizing capacities prior to fractionation.

Citation

Negm, O. H., MacKenzie, B., Hamed, M., Ahmad, O., Shone, C. C., Humphreys, D., …Monaghan, T. M. (2017). Protective antibodies against Clostridium difficile are present in intravenous immunoglobulin and are retained in humans following its administration. Clinical and Experimental Immunology, 188(3), 437-443. https://doi.org/10.1111/cei.12946

Journal Article Type Article
Acceptance Date Feb 14, 2017
Online Publication Date Mar 16, 2017
Publication Date 2017-06
Deposit Date Jul 19, 2017
Publicly Available Date Jul 19, 2017
Journal Clinical & Experimental Immunology
Print ISSN 0009-9104
Electronic ISSN 1365-2249
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 188
Issue 3
Pages 437-443
DOI https://doi.org/10.1111/cei.12946
Keywords Antibodies, Clostridium difficile, Intravenous immunoglobulin
Public URL http://eprints.nottingham.ac.uk/id/eprint/44226
Publisher URL http://onlinelibrary.wiley.com/doi/10.1111/cei.12946/abstract;jsessionid=14EC0238885E82ADDB0DD2660A14B365.f03t03
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingh.../end_user_agreement.pdf
Additional Information This is the peer reviewed version of the following article: Negm, O. H., MacKenzie, B., Hamed, M. R., Ahmad, O. A. J., Shone, C. C., Humphreys, D. P., Ravi Acharya, K., Loscher, C. E., Marszalowska, I., Lynch, M., Wilcox, M. H. and Monaghan, T. M. (2017), Protective antibodies against Clostridium difficile are present in intravenous immunoglobulin and are retained in humans following its administration. Clin Exp Immunol, 188: 437–443, which has been published in final form at http://onlinelibrary.wi...B0DD2660A14B365.f03t03. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.

Files

Protective antibodies against Clostridium difficile are present in intravenous immunoglobulin and are retained in humans following its administration .pdf (814 Kb)
PDF

Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf





You might also like



Downloadable Citations