Transmission of Hepatitis B core Antibody and Galactomannan Enzyme Immunoassay positivity via immunoglobulin products: a comprehensive analysis
Isobel Ramsay1,2, Rebecca L. Gorton3, Mauli Patel4, Sarita Workman5, Andrew Symes5, Tanzina Haque1, Dianne Irish1, Suranjith L. Seneviratne5,6, Siobhan O. Burns5,6, Emmanuel Wey7, and David M. Lowe5,6
1Department of Virology, Royal Free London NHS Foundation Trust, London, UK
2Department of Microbiology, Addenbrooke's Hospital NHS Foundation Trust, Cambridge, UK
3Department of Microbiology, Health Services Laboratory (HSL), Royal Free Hospital, London, UK
4Department of Virology, Health Services Laboratory (HSL), Royal Free Hospital, London, UK
5Department of Clinical Immunology, Royal Free London NHS Foundation Trust, London, UK
6Institute of Immunity and Transplantation, University College London, Royal Free Campus, London, UK
7Department of Microbiology, Royal Free London NHS Foundation Trust, London, UK
Corresponding author: Dr David Lowe, Institute of Immunity and Transplantation, University College London, Royal Free Campus, London, NW3 2QG, UK. d.lowe{at}ucl.ac.uk
Abstract
Background. Therapeutic immunoglobulins are used as replacement or immunomodulatory therapy, but can transmit clinically important molecules. We investigated Hepatitis B virus (HBV) antibodies and galactomannan enzyme immunoassay (GM-EIA) positivity. Detection of HBV core antibody may prompt antiviral prophylaxis when commencing therapy such as rituximab; a positive GM-EIA result prompts investigation or treatment for invasive fungal disease.
Methods. Cross-sectional analysis of HBV serology in 80 patients established (>6 months) on immunoglobulin therapy; prospective analysis of HBV serology in 16 patients commencing intravenous immunoglobulin (IVIG); pre- and post-infusion analysis of GM-EIA in 37 patients receiving IVIG.
Results. Pre-IVIG, 9/80 patients tested positive for HBV surface antibody and 1/80 tested equivocal for HBV core antibody. On IVIG, 79/79 tested positive for surface antibody, 37/80 tested positive for core antibody and 10/80 tested equivocal for core antibody. There were significant differences by product, but among patients receiving products which appear to transmit core antibody, negative results correlated with lower surface antibody titres and longer time since infusion suggesting a simple concentration effect. There was a progressive increase with each infusion in the percentage of patients testing positive for HBV core antibody among patients newly commencing IVIG. Some patients ‘sero-reverted’ to negative during therapy. Certain IVIG products tested positive for GM-EIA and there were rises in index values in corresponding patient samples from pre- to post-infusion. Overall, 5/37 patient samples pre-infusion and 15/37 samples post-infusion tested positive for GM-EIA.
Conclusions. HBV antibodies and GM-EIA positivity are common in patients receiving IVIG and confound diagnostic results.
伊泽贝尔Ramsay1,2，丽贝卡L. Gorton3，Mauli Patel4，萨里塔Workman5，安德鲁Symes5，Tanzina Haque1，戴安娜Irish1，Suranjith L. Seneviratne5,6，西沃恩O. Burns5,6，灵光Wey7和David M. Lowe5,6