title: Transmission of Hepatitis B Core Antibody and Galactomannan Enzyme Immunoassay Positivity via Immunoglobulin Products: A Comprehensive Analysis.
abstract: 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.
  
  
  
  We performed a 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); and pre- and post-infusion analysis of GM-EIA in 37 patients receiving IVIG.
  
  
  
  Pre-IVIG, 9 of 80 patients tested positive for HBV surface antibody and 1 of 80 tested equivocal for HBV core antibody. On IVIG, 79 of 79 tested positive for surface antibody, 37 of 80 tested positive for core antibody, and 10 of 80 tested equivocal for core antibody. There were significant differences by product, but among patients receiving products that appear to transmit core antibody, negative results correlated with lower surface antibody titers 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 "seroreverted" 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 of 37 patient samples pre-infusion and 15 of 37 samples post-infusion tested positive for GM-EIA.
  
  
  
  HBV antibodies and GM-EIA positivity are common in patients receiving IVIG and confound diagnostic results.
authors.affiliation: Department of Virology, Royal Free London National Health Service (NHS) Foundation Trust.|Department of Microbiology, Addenbrooke's Hospital NHS Foundation Trust, Cambridge.
authors.forename: Isobel
authors.initials: I
authors.lastname: Ramsay
authors.affiliation: Department of Microbiology.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Gorton
authors.affiliation: Department of Virology, Health Services Laboratory, Royal Free Hospital.
authors.forename: Mauli
authors.initials: M
authors.lastname: Patel
authors.affiliation: Department of Clinical Immunology, Royal Free London NHS Foundation Trust.
authors.forename: Sarita
authors.initials: S
authors.lastname: Workman
authors.affiliation: Department of Clinical Immunology, Royal Free London NHS Foundation Trust.
authors.forename: Andrew
authors.initials: A
authors.lastname: Symes
authors.affiliation: Department of Virology, Royal Free London National Health Service (NHS) Foundation Trust.
authors.forename: Tanzina
authors.initials: T
authors.lastname: Haque
authors.affiliation: Department of Virology, Royal Free London National Health Service (NHS) Foundation Trust.
authors.forename: Dianne
authors.initials: D
authors.lastname: Irish
authors.affiliation: Department of Clinical Immunology, Royal Free London NHS Foundation Trust.|Institute of Immunity and Transplantation, University College London, Royal Free Campus.
authors.forename: Suranjith L
authors.initials: SL
authors.lastname: Seneviratne
authors.affiliation: Department of Clinical Immunology, Royal Free London NHS Foundation Trust.|Institute of Immunity and Transplantation, University College London, Royal Free Campus.
authors.forename: Siobhan O
authors.initials: SO
authors.lastname: Burns
authors.affiliation: Department of Microbiology, Royal Free London NHS Foundation Trust, United Kingdom.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Wey
authors.affiliation: Department of Clinical Immunology, Royal Free London NHS Foundation Trust.|Institute of Immunity and Transplantation, University College London, Royal Free Campus.
authors.forename: David M
authors.initials: DM
authors.lastname: Lowe
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003430:Cross-Sectional Studies; D005189:False Positive Reactions; D005260:Female; D005690:Galactose / Q000031:analogs & derivatives; D006509:Hepatitis B / Q000276:immunology*; D006510:Hepatitis B Antibodies / Q000097:blood*; D006512:Hepatitis B Core Antigens / Q000097:blood*; D006801:Humans; D007116:Immunization, Passive; D007124:Immunoenzyme Techniques / Q000379:methods* / Q000592:standards; D016756:Immunoglobulins, Intravenous / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008351:Mannans; D008875:Middle Aged; D055815:Young Adult
chemical_list: D006510:Hepatitis B Antibodies; D006512:Hepatitis B Core Antigens; D016756:Immunoglobulins, Intravenous; D008351:Mannans; C012990:galactomannan; D005690:Galactose
keywords: IVIG; galactomannan; hepatitis B; immunoglobulin; serology