Absence of Persistent Hepatitis E Virus Infection in Antibody-Deficient Patients Is Associated With Transfer of Antigen-Neutralizing Antibodies From Immunoglobulin Products

Ankcorn, Mike; Moreira, Fernando; Ijaz, Samreen; Symes, Andrew; Buckland, Matthew; Workman, Sarita; Tedder, Richard S.; Lowe, David M.

doi:10.1093/infdis/jiy504

Cited by 5 publications

(5 citation statements)

References 40 publications

(49 reference statements)

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“…A recent study determined HEV antibody titers in IG preparations and found all products reactive for HEV IgG 24 . This included a lot of KIOVIG, for which a titer of approximately 2.8 U/mL was determined, however, without information on geographic origin of the plasma used in manufacture, 24 whereas the titer of the KIOVIG lot fractionated exclusively from EU plasma that was used in the PBS experiment reported here was 7.6 U/mL.…”

Section: Discussionmentioning

confidence: 93%

“…The lower HEV prevalence in the United States was reflected in HEV antibody titers below the LOD in the eight US plasma‐derived intermediates tested, whereas only one in six EU plasma‐derived intermediates was below the LOD and HEV titers of 1.02 and 1.32 U/mL were determined for five EU plasma‐derived intermediates. A recent study determined HEV antibody titers in IG preparations and found all products reactive for HEV IgG 24 . This included a lot of KIOVIG, for which a titer of approximately 2.8 U/mL was determined, however, without information on geographic origin of the plasma used in manufacture, 24 whereas the titer of the KIOVIG lot fractionated exclusively from EU plasma that was used in the PBS experiment reported here was 7.6 U/mL.…”

Section: Discussionmentioning

confidence: 93%

“…Effective HEV removal during nanofiltration suggests that the substantially higher HEV antibody titers in final‐product IG additionally contribute to HEV clearance through neutralization. A recent study reported the presence of HEV antibodies in all IG products investigated and suggested passive seroprotection from persistent HEV infection in immune‐deficient patients as associated with the presence of HEV antibodies in these IG products 24 . The HEV neutralization potency of IG lots manufactured from plasma collected in the European Union or the United States would still benefit from further studies.…”

Section: Discussionmentioning

confidence: 99%

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Antibody‐enhanced hepatitis E virus nanofiltration during the manufacture of human immunoglobulin

et al. 2020

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Background: Circulation of hepatitis E virus (HEV) in areas where plasma is sourced for the manufacture of plasma-derived medicinal products (PDMPs) has prompted verification of HEV clearance. HEV exists as quasi lipid-enveloped (LE) and non-lipid-enveloped (NLE) forms, which might be of relevance for HEV clearance from manufacturing processes of antibody-containing PDMPs with solvent/detergent (S/D) treatment upstream of further clearance steps. Study Design and Methods: Presence of different HEV particles in stocks used in clearance studies was investigated, with nanofilters graded around the assumed HEV particle sizes and by gradient centrifugation. HEV removal by 35-nm nanofiltration was investigated in the presence or absence of HEV antibodies, in buffer as well as in immunoglobulin (IG) manufacturing process intermediates. Results: HEV particles consistent with LE, NLE, and an "intermediate" (IM) phenotype, obtained after S/D treatment, were seen in different HEV stocks. In the absence of HEV antibodies, log reduction factors (LRFs) of 4.0 and 2.5 were obtained by 35-nm nanofiltration of LE and IM HEV, consistent with the larger and smaller sizes of these phenotypes. Addition of HEV antibodies enhanced IM HEV removal around 1000-fold (LRF, 5.6). Effective (LRF, >4.8 and >4.0) HEV removal was obtained for the nanofiltration processing step for IG intermediates with varying HEV antibody content. Conclusion: HEV spikes used in clearance studies should be carefully selected, as differences in physicochemical properties might affect HEV clearance. Antibody-mediated enhancement of HEV nanofiltration was

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

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Antibody‐enhanced hepatitis E virus nanofiltration during the manufacture of human immunoglobulin

et al. 2020

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“…Hepatitis E virus appears to have a lower prevalence with fewer documented reports within inborn errors of immunity, which may be associated with the neutralising antibody in many infused immunoglobulin products [80]. There has been a recent case report of CVID patient with acute hepatitis owing to hepatitis E, which highlights the importance of maintaining vigilance even in those established on immunoglobulin replacement [81].…”

Section: Viral Infectionsmentioning

confidence: 99%

Differential Diagnosis: Hepatic Complications in Inborn Errors of Immunity

Zinser,

Tan,

Kim

et al. 2023

JCM

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Inborn errors of immunity (IEIs) are a heterogeneous group of diverse clinical and genetic phenotypes that have an estimated combined prevalence as high as 1/1000. Increased risk of frequent, severe, or opportunistic infections is a common feature of IEIs, but there are also diverse immune-mediated, non-infective complications that are associated with significant morbidity and mortality. As patient survival increases, these are becoming more apparent within the liver. Hepatic involvement of IEIs may not only manifest as infections, but also nodular regenerative hyperplasia, granulomatous disease, autoimmune hepatitis and malignancy. As therapeutic options for patients are expanding, with both pharmaceutical treatments as well as haematopoietic stem cell transplant (HSCT), iatrogenic liver injury is increasingly common and important to identify. This review article summarises the spectrum of hepatic complications seen in IEIs, and highlights the challenges of management within this patient cohort, where immunosuppression is poorly tolerated. Early recognition and prompt diagnosis of potential hepatic complications is therefore crucial in ensuring potentially reversible causes are treated, but significant uncertainty remains regarding best practice for many features of immune dysregulation with limited high-quality evidence.

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“…Other chronic viral hepatitides are described less commonly in these patient cohorts. We recently screened our antibody‐deficient patients for the presence of chronic hepatitis E but identified no patients, which may correlate with the presence of efficient neutralising antibody in many of the infused immunoglobulin products …”

Section: Hepacivirusesmentioning

confidence: 99%

Viral infection in primary antibody deficiency syndromes

Jones

Buckland

Breuer

et al. 2019

Reviews in Medical Virology

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Patients with primary antibody deficiency syndromes such as X-linked agammaglobulinemia (XLA) and common variable immunodeficiency (CVID) are at increased risk of severe and invasive infection. Viral infection in these populations has been of increasing interest as evidence mounts that viruses contribute significant morbidity and mortality: this is mediated both directly and via aberrant immune responses.We explain the importance of the humoral immune system in defence against viral pathogens before highlighting several significant viral syndromes in patients with antibody deficiency.We explore historical cases of hepatitis C via contaminated immunoglobulin products, the predisposition to invasive enteroviral infections, prolonged excretion of vaccinederived poliovirus, the morbidity of chronic norovirus infection, and recent literature revealing the importance of respiratory viral infections. We discuss evidence that herpesviruses may play a role in driving the inflammatory disease seen in a subset of patients. We explore the phenomenon of within-host evolution during chronic viral infection and the potential emergence of new pathogenic strains. We highlight novel and emerging viruses identified via deep sequencing techniques. We describe the treatment strategies that have been attempted in all these scenarios and the urgent outstanding questions for research.

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Absence of Persistent Hepatitis E Virus Infection in Antibody-Deficient Patients Is Associated With Transfer of Antigen-Neutralizing Antibodies From Immunoglobulin Products

Abstract: The risk of persistent HEV infection in patients with antibody deficiency appears extremely low. This may be due to passive seroprotection afforded by the ubiquitous presence of anti-HEV in immunoglobulin replacement products.

Cited by 5 publications

References 40 publications

Antibody‐enhanced hepatitis E virus nanofiltration during the manufacture of human immunoglobulin

Antibody‐enhanced hepatitis E virus nanofiltration during the manufacture of human immunoglobulin

Differential Diagnosis: Hepatic Complications in Inborn Errors of Immunity

Viral infection in primary antibody deficiency syndromes

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