Envelope-Specific IgG3 and IgG1 Responses Are Associated with Clearance of Acute Hepatitis C Virus Infection

Walker, Melanie R.; Eltahla, Auda A.; Mina, Michael; Li, Hui; Lloyd, Andrew R.; Bull, Rowena A.

doi:10.3390/v12010075

Cited by 22 publications

(47 citation statements)

References 81 publications

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“…Previous studies have demonstrated that when compared with HCs, serum IgG1 and IgG3 levels were higher in virus-infected individuals (48). In the present study, IgG1/IgG levels were significantly increased in viral liver disease group when compared with HCs.…”

Section: Discussionsupporting

confidence: 51%

Levels of serum IgG subclasses in patients with liver disease: A retrospective study

et al. 2020

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Viral and alcoholic liver disease, drug induced liver disease (DILD), primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) are among the most common liver diseases observed in clinical practice. These diseases lack unique clinical characteristics at the beginning of pathogenesis, which renders specific diagnosis difficult. Immunoglobulin G (IgG) subclasses are the main isoform of antibodies that can be found in the serum that serve important protective roles in immunity. The present study aimed to investigate the serum IgG subclass distribution in patients with the five common liver diseases aforementioned. The present study retrospectively recorded and analyzed the serum IgG subclass levels of different patients, who were grouped according to their clinical diagnosis. Serum IgG subclass levels were measured using immunonephelometric assays. IgG3 levels were found to be significantly increased whereas IgG4 levels were significantly decreased in patients with PBC. In patients with AIH, IgG1 levels were significantly increased. By contrast, IgG1/IgG level ratios in patients with viral liver disease were significantly increased. No clear pattern in the distribution characteristics of IgG subclasses could be observed in cohorts with alcoholic liver disease and DILD in the present study. Additionally, model for end-stage liver disease scores regarding IgG1 in patients with AIH shared a synergistic relationship. Anti-mitochondrial antibody subtype M2 (AMA-M2) and IgG3 in patients with PBC demonstrated a synergistic relationship. These results suggested that IgG subclasses may be used as biomarkers to further the understanding of liver disease, which could allow for early diagnosis.

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Section: Discussionsupporting

confidence: 51%

Levels of serum IgG subclasses in patients with liver disease: A retrospective study

et al. 2020

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“…Surprisingly, however, anti‐E IgA was significantly associated with HESN individuals when compared to the pre‐infection time point of incident individuals. In our previous report of serological responses during primary HCV infection, very few subjects had detectable anti‐HCV E IgA responses and there was no association with clearance 40 . Given the recognized role of polymeric IgA (pIgA) in mucosal protection, and the previous analysis of incident case samples from this cohort showing elevated serum levels of pIgA, 48 it may be of interest to further characterize these IgA responses.…”

Section: Discussionmentioning

confidence: 85%

“…These responses were almost exclusively in the IgG2 subclass. This finding is noteworthy as IgG2 responses are rare in primary HCV infection, 40 but do have unique functional characteristics of potential relevance to protective immunity. IgG2 antibodies are recognized to bind glycans independent of T‐cell help (typically targeting bacterial polysaccharides, but also viral glycans) 43,44 .…”

Section: Discussionmentioning

confidence: 89%

“…However, neutralizing antibodies are also commonly found in chronic HCV infections, and even when found in those who clear primary infection they do not necessarily protect from reinfection 14,39 . In our recent study of subjects with early primary HCV infection, all subjects had detectable E‐specific IgG responses, but clearance of the infection was associated with the early development of IgG1 and IgG3 isotype responses, 40 along with autologous transmitted‐founder virus‐specific neutralization, 38 highlighting the link between the timing and IgG subclass response elicited and infection outcome. In the present study, a significant minority of the carefully identified HESN cases had repeatedly detectable IgG responses against gt1 or gt3 E (which constitute approximately 90% of incident and prevalent genotypes in Australia) 41,42 .…”

Section: Discussionmentioning

confidence: 91%

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Anti‐envelope antibody responses in highly exposed seronegative individuals may be associated with protection from HCV infection

Mina

Underwood

Eltahla

et al. 2020

Journal of Viral Hepatitis

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In rare cases, individuals with a history of long‐term injecting drug use remain seronegative and aviraemic, despite prolonged and likely repeated exposure to Hepatitis C virus (HCV) through high‐risk behaviour. We describe anti‐HCV Envelope (E) antibody responses in a prospective cohort of carefully defined highly exposed but uninfected subjects (HESN) and comparison subjects who were also high risk and uninfected, but rapidly became HCV infected (Incident). Longitudinally collected samples from HESN cases (n = 22) were compared to Incident controls (n = 22). IgG, IgM and IgA from sera were tested by ELISA to genotype 1a and 3a E glycoproteins, and recombinant genotype 1a E2 antigen. IgG subclass isotyping was performed for those positive for IgG. Virus‐neutralizing activity was assessed on HCV pseudoparticles, and HCV E–specific B cells analysed using flow cytometry. A significant minority of HESN cases (n = 10; 45%) had anti‐E, predominantly in the IgG2 subclass, which was not found in the pre‐infection time point of the Incident cases (n = 1; 5%). A subset of the HESN subjects also had neutralizing activity and HCV‐specific B cells detected significantly more than Incident cases pre‐infection. In conclusion, the HESN phenotype is associated with IgG2 anti‐E antibodies, neutralization activity and HCV E–specific memory B cells. These findings suggest that HESN subjects may be resistant to HCV infection through humoral immune‐mediated mechanisms.

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“…These data suggested that the earlier and higher the NP-specific IgG and IgM appeared, the more likely HFRS developed mild disease. Prior studies have suggested that the deficiency of virus-specific IgG was associated with persistent viremia [22,23]. Hence, we examined plasma viral loads in HFRS patients by quantitative RT-PCR.…”

Section: Effective Np-specific Antibody Responses Associated With Htnmentioning

confidence: 98%

Rapid humoral immune responses are required for recovery from haemorrhagic fever with renal syndrome patients

Quan

Xing

et al. 2020

Emerging Microbes & Infections

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Haemorrhagic fever with renal syndrome (HFRS) following Hantaan virus (HTNV) infection displays variable clinical signs. Humoral responses elicited during HTNV infections are considered important, however, this process remains poorly understood. Herein, we have investigated the phenotype, temporal dynamics, and characteristics of B-cell receptor (BCR) repertoire in an HFRS cohort. The serological profiles were characterized by a lowered expression level of nucleoprotein (NP)-specific antibody in severe cases. Importantly, B-cell subsets were activated and proliferated within the first two weeks of symptom onset and moderate cases reacted more rapidly. BCR analysis in the recovery phase revealed a dramatic increase in the immunoglobulin gene diversity which was more significantly progressed in moderate infections. In severe cases, B-cell-related transcription was lower with inflammatory sets overactivated. Taken together, these data suggest the clinical signs and disease recovery in HFRS patients were positively impacted by rapid and efficacious humoral responses.

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Envelope-Specific IgG3 and IgG1 Responses Are Associated with Clearance of Acute Hepatitis C Virus Infection

Cited by 22 publications

References 81 publications

Levels of serum IgG subclasses in patients with liver disease: A retrospective study

Levels of serum IgG subclasses in patients with liver disease: A retrospective study

Anti‐envelope antibody responses in highly exposed seronegative individuals may be associated with protection from HCV infection

Rapid humoral immune responses are required for recovery from haemorrhagic fever with renal syndrome patients

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