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

Negm, Ola H. and MacKenzie, B. and Hamed, M.R. and Ahmad, O.A.J. and Shone, Clifford C. and Humphreys, D.P. and Acharya, K. Ravi and Loscher, Christine E. and Marszalowska, Izabela and Lynch, Mark and Wilcox, Mark H. and Monaghan, Tanya 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). pp. 437-443. ISSN 1365-2249

[img] PDF - Repository staff only - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
Download (414kB)
[img] PDF - Repository staff only until 16 March 2018. - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
Download (814kB)

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.

Item Type: Article
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.wiley.com/doi/10.1111/cei.12946/abstract;jsessionid=14EC0238885E82ADDB0DD2660A14B365.f03t03. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Keywords: Antibodies, Clostridium difficile, Intravenous immunoglobulin
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences
University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Division of Medical Sciences and Graduate Entry Medicine
University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Nottingham Digestive Diseases Centre
Identification Number: 10.1111/cei.12946
Depositing User: Negm, Ola
Date Deposited: 19 Jul 2017 08:15
Last Modified: 23 Aug 2017 06:26
URI: http://eprints.nottingham.ac.uk/id/eprint/44226

Actions (Archive Staff Only)

Edit View Edit View