scholarly journals Peripheral Blood Mononuclear Cell Gene Expression Remains Broadly Altered Years after Successful Interferon-Based Hepatitis C Virus Treatment

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Paul Ravi Waldron ◽  
Mark Holodniy

Background. Inflammatory gene expression in peripheral blood mononuclear cells (PBMCs) is altered in chronic Hepatitis C Virus (HCV) infection. Duration of changes after pegylated interferon- (peg-IFN-) based HCV treatment is unclear.Methods. PBMC mRNA expression of 184 inflammatory response genes was analyzed (nCounter GX Human Inflammation Kit, Nanostring) from peg-IFN treatment nonresponders (NR,n=18), sustained virologic responders (SVR,n=22), and spontaneous clearers (SC,n=15). Logistic regression was used for comparison.Results. Median time from last treatment was 2 and 2.7 years in SVR and NR, respectively (p= NS). Mean mRNA counts were significantly different for 42 and 29 genes comparing SVR to SC patients and NR to SC, respectively, and no genes comparing SVR to NR. Differential expression of 24 genes was significantly different in both SVR and NR groups compared to SC. Among these 24 acute and chronic inflammatory cascade genes, significant upregulation was noted for proinflammatory transcription regulatorsFos,CEBPB, andMyD88in SVR and NR compared to SC.HDAC4was significantly downregulated in SVR and NR compared to the SC group.Conclusions. PBMC inflammatory gene expression patterns in SVR resemble NR more than SC patients. A generalized inflammatory response persists in PBMCs long after successful peg-IFN treatment for HCV infection.

2013 ◽  
Vol 74 (12) ◽  
pp. 1559-1562 ◽  
Author(s):  
Joanna Jabłońska ◽  
Jakub Ząbek ◽  
Agnieszka Pawełczyk ◽  
Natalia Kubisa ◽  
Maria Fic ◽  
...  

Pathogens ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1519
Author(s):  
Sahar Essa ◽  
Iqbal Siddique ◽  
Motaz Saad ◽  
Raj Raghupathy

This study investigated the influence of Hepatitis C virus (HCV) infection on the cytokine production profiles of the peripheral blood monoculear cells (PBMC) and neutrophils in chronically naïve HCV-infected patients. Seventy-five genotype-4 naïve HCV-infected patients (HCV+) and healthy subjects (HCV−) were enrolled. The neutrophils and the PBMC were separated by density gradient sedimentation and stimulated with a mitogen. The culture supernatants were evaluated for levels of IFN-α, IFN-γ, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12, and TNF-α using anti-cytokine antibody MACSPlex capture beads. The PBMC cytokine profiles of HCV+ patients showed significantly lower mean values for IFN-γ, IL-2, IL-6, IL-9, and IL-10 (p < 0.0001) as compared to HCV− subjects. In contrast, HCV+ patients showed higher mean levels of PBMC cytokine values for IL-5 and TNF-α (p < 0.0001). As for neutrophils, HCV+ patients showed significantly lower mean levels of IFN-α, IFN-γ, IL-2, IL-4, IL-6, IL-9, and IL-10 (p < 0.0001). In contrast, the neutrophils from HCV+ patients showed higher mean levels of IL-5, IL-12, and TNF-α (p < 0.0001). Th1–Th2 cytokine ratios suggested a lower Th1 bias in HCV+ subjects as compared to HCV− subjects. Our results suggest that chronic HCV infection brings about an immunomodulatory effect not only on neutrophils, but also to a lower extent on PBMCs


Blood ◽  
1993 ◽  
Vol 82 (12) ◽  
pp. 3701-3704 ◽  
Author(s):  
C Ferri ◽  
M Monti ◽  
L La Civita ◽  
G Longombardo ◽  
F Greco ◽  
...  

A striking association between hepatitis C virus (HCV) infection and mixed cryoglobulinemia (MC) has been shown; thus, HCV seems to play an important etiopathogenetic role in this lymphoproliferative disorder. Because HCV is both a hepatotropic and lymphotropic virus, this study aimed to investigate the prevalence of HCV infection of peripheral blood mononuclear cells (PBMCs) in a series of 16 patients with type II (IgMk) MC. Antibodies against HCV were detected by commercially available kits (Second Generation Chiron enzyme-linked immunosorbent assay [ELISA] and recombinant-based immunoblot assay [RIBA]), and the presence of HCV RNA was evaluated in both sera and isolated PBMCs using the polymerase chain reaction technique. A previous exposure to HCV was shown by ELISA and confirmed by RIBA in all cases (100%). Moreover, HCV RNA was present in the sera of 8 of 16 patients (50%), whereas its frequency markedly increased (13 of 16 [81%]) when genomic sequences were detected in peripheral lymphocytes. HCV RNA was never detected in the PBMCs of 20 control subjects. These findings showed that HCV infection, alone or in combination with other factors, may be responsible for the clonal B-cell expansion underlying the systemic manifestations of MC, and may explain the appearance of a malignant non- Hodgkin's lymphoma in some subjects.


Blood ◽  
1993 ◽  
Vol 82 (12) ◽  
pp. 3701-3704 ◽  
Author(s):  
C Ferri ◽  
M Monti ◽  
L La Civita ◽  
G Longombardo ◽  
F Greco ◽  
...  

Abstract A striking association between hepatitis C virus (HCV) infection and mixed cryoglobulinemia (MC) has been shown; thus, HCV seems to play an important etiopathogenetic role in this lymphoproliferative disorder. Because HCV is both a hepatotropic and lymphotropic virus, this study aimed to investigate the prevalence of HCV infection of peripheral blood mononuclear cells (PBMCs) in a series of 16 patients with type II (IgMk) MC. Antibodies against HCV were detected by commercially available kits (Second Generation Chiron enzyme-linked immunosorbent assay [ELISA] and recombinant-based immunoblot assay [RIBA]), and the presence of HCV RNA was evaluated in both sera and isolated PBMCs using the polymerase chain reaction technique. A previous exposure to HCV was shown by ELISA and confirmed by RIBA in all cases (100%). Moreover, HCV RNA was present in the sera of 8 of 16 patients (50%), whereas its frequency markedly increased (13 of 16 [81%]) when genomic sequences were detected in peripheral lymphocytes. HCV RNA was never detected in the PBMCs of 20 control subjects. These findings showed that HCV infection, alone or in combination with other factors, may be responsible for the clonal B-cell expansion underlying the systemic manifestations of MC, and may explain the appearance of a malignant non- Hodgkin's lymphoma in some subjects.


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