Autoantibodies to cytoplasmic rods and rings in patients with hepatitis C virus infection treated with direct-acting antivirals: The role of prior treatment with interferon plus ribavirin

Alsius, Mercè; Ferri, María José; Buxó, María; López, Carme; Serra, Isabel; Queralt, Xavier; Acero, Doroteo

doi:10.1016/j.gastrohep.2018.08.005

Cited by 7 publications

(6 citation statements)

References 13 publications

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“…One of the interesting findings from in vitro cell‐based models is that ribavirin treatment can strongly induce the rapid formation of helical polymers composed of stacked IMP dehydrogenase (IMPDH) octamers (Fig EV5A ), referred to as “rod and ring (RR)” structures (Thomas et al , 2012 ; Keppeke et al , 2019 ) (Fig EV5B ). Anti‐RR antibodies have been detected in HCV patients only after ribavirin treatment, not prior to treatment (Alsius et al , 2019 ). This implies that the RR structure could be used as an indicator of ribavirin efficacy.…”

Section: Resultsmentioning

confidence: 99%

SARS‐CoV‐2–host proteome interactions for antiviral drug discovery

Liu

Huuskonen

Laitinen

et al. 2021

Molecular Systems Biology

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Treatment options for COVID-19, caused by SARS-CoV-2, remain limited. Understanding viral pathogenesis at the molecular level is critical to develop effective therapy. Some recent studies have explored SARS-CoV-2-host interactomes and provided great resources for understanding viral replication. However, host proteins that functionally associate with SARS-CoV-2 are localized in the corresponding subnetwork within the comprehensive human interactome. Therefore, constructing a downstream network including all potential viral receptors, host cell proteases, and cofactors is necessary and should be used as an additional criterion for the validation of critical host machineries used for viral processing. This study applied both affinity purification mass spectrometry (AP-MS) and the complementary proximity-based labeling MS method (BioID-MS) on 29 viral ORFs and 18 host proteins with potential roles in viral replication to map the interactions relevant to viral processing. The analysis yields a list of 693 hub proteins sharing interactions with both viral baits and host baits and revealed their biological significance for SARS-CoV-2. Those hub proteins then served as a rational resource for drug repurposing via a virtual screening approach. The overall process resulted in the suggested repurposing of 59 compounds for 15 protein targets. Furthermore, antiviral effects of some candidate drugs were observed in vitro validation using image-based drug screen with infectious SARS-CoV-2. In addition, our results suggest that the antiviral activity of methotrexate could be associated with its inhibitory effect on specific protein-protein interactions.

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Section: Resultsmentioning

confidence: 99%

SARS‐CoV‐2–host proteome interactions for antiviral drug discovery

Liu

Huuskonen

Laitinen

et al. 2021

Molecular Systems Biology

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“…The clinical significance of other required fluorescence patterns are not clear yet [8,9] . The multivariate analysis showed significant associations (7.4%–29.6%) between anti-RR pattern and “time of exposure to interferon and ribavirin” [10] . The combination of anti-cytoplasmic autoantibody and Jo-1 showed high sensitivity (92%) and specificity (89%) for the identification of anti-synthetase syndrome patients [11] .…”

Section: Introductionmentioning

confidence: 98%

“…[ 8 , 9 ] The multivariate analysis showed significant associations (7.4%–29.6%) between anti-RR pattern and “time of exposure to interferon and ribavirin”. [ 10 ] The combination of anti-cytoplasmic autoantibody and Jo-1 showed high sensitivity (92%) and specificity (89%) for the identification of anti-synthetase syndrome patients. [ 11 ] In the elderly group (60–76 years old), the positive rate of cytoplasmic patterns accounted for 17.2% of the total Thais healthy participants, second only to the spot pattern (20.6%), suggesting that ANA cytoplasmic patterns were related to the age of patients.…”

Section: Introductionmentioning

confidence: 99%

Clinical significance of HEp-2 cell cytoplasmic patterns in anti-neutrophil cytoplasmic antibody associated vasculitis

Zhang

Bao

et al. 2022

Medicine

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The study was to investigate the clinical characteristics and significance of antinuclear antibody (ANA) cytoplasmic patterns in ANCA-associated vasculitis (AAV) from Southwest China. A retrospective study including 232 AAV patients from Peoples Hospital of Deyang City was performed. These included 115 patients with ANA cytoplasmic pattern as observation group and 117 patients without ANA cytoplasmic pattern as control group. Chest involvement (60.00 vs 46.15, P = .035), cardiovascular involvement (5.21 vs 29.91, P < .001), and renal involvement (37.39 vs 77.78, P = .001) were different between groups. Total protein (69.55 vs 64.01, P < .001), triglyceride (1.41 vs 1.18, P = .023), mean cell volume (89.76 vs 87.59, P = .040), and estimated glomerular filtration rate (76.67 vs 50.87, P = .035) were higher in ANA cytoplasmic patterns group. Creatinine (73.00 vs 117.50, P = .011), white blood cell (6.93 vs 8.86, P = .001), platelet (196.0 vs 239.0, P = .017), anti-myeloperoxidase (2.44 vs 3.42, P = .042), and anti-proteinase 3 (1.00 vs 4.93, P = .007) were lower in this group. In multivariate analysis, creatinine (odds ratio [OR] = 1.21, 95% confidence interval [CI]: 1.06–1.38), triglyceride (OR = 1.97, 95% CI: 1.10–3.48), and anti-myeloperoxidase (OR = 1.64, 95% CI: 1.37–1.95) were independent risk factors of AAV renal involvement. Total protein (OR = .95, 95% CI: 0.91–0.99) was an independent protective factor of AAV renal involvement. Chi-square test showed that speckled pattern was different among anti-neutrophil cytoplasmic antibody patterns ( χ 2 = 18.526, P < .001). In summary, HEp-2 cell cytoplasmic patterns have certain clinical significance in AAV, which is a new exploration of the clinical value of ANA.

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“…[ 6 ] It was reported that anti-RR antibodies were mainly found in HCV patients treated with interferon-α/ribavirin (IFN-α/RBV) combination therapy. [ 7 – 9 ]…”

Section: Introductionmentioning

confidence: 99%

“…[6] It was reported that anti-RR antibodies were mainly found in HCV patients treated with interferon-a/ribavirin (IFNa/RBV) combination therapy. [7][8][9] Early studies revealed that 2 key enzymes in the nucleotide synthetic pathway such as cytidine triphosphate synthase 1 (CTPS1) and inosine monophosphate dehydrogenase 2 (IMPDH2) were highly enriched in anti-RR antibodies. [4,10] But 2 years later, more research showed that IMPDH2 was indeed the main target of anti-RR while CTPS1 was an unlikely 1.…”

Section: Introductionmentioning

confidence: 99%

The value of anti-rods and rings antibodies in patients with nonhepatitis virus infection

Zhang¹,

Ji²,

Yang³

et al. 2021

Medicine

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The aim of this study was to retrospectively investigate the clinical significance of anti-rods and rings (anti-RR) antibodies in nonhepatitis virus infection patients from Southwest China. Anti-RR antibodies were determined by indirect immunofluorescence assay in a group of 19,935 individuals with antinuclear antibodies test from January 2017 to December 2019. The laboratory and clinical data were collected. Finally, 66 samples with anti-RR antibodies (0.33%) were detected. In Wilcoxon rank sum test, gamma glutamyl transferase ( Z = −3.364, P = .001), alpha-l-fucosidase (AFU) ( Z = −2.312, P = .021), uric acid ( Z = −1.634, P = .047) and red blood cell distribution width ( Z = −2.285, P = .022) were higher in metabolic disease group than nonmetabolic disease group. In independent-samples t test, endogenous creatinine clearance was higher in metabolic disease group than nonmetabolic disease group ( t = 2.061, P = .045). During the follow-up period of 37 patients with anti-RR antibodies for 1 to 60 months, the titers of anti-RR were significantly increased in the metabolic disease group ( Z = −2.346, P = .019). In binary logistic regression analysis, triglycerides (odds ratio 3.679, 95% confidence interval 1.467–24.779, P = .048) was associated with elevated titers of anti-RR antibodies. In summary, anti-RR in non-hepatitis patients may be a manifestation of metabolic disorders, and has a certain correlation with routine laboratory indicators, which is worthy of the attention from clinicians.

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Autoantibodies to cytoplasmic rods and rings in patients with hepatitis C virus infection treated with direct-acting antivirals: The role of prior treatment with interferon plus ribavirin

Cited by 7 publications

References 13 publications

SARS‐CoV‐2–host proteome interactions for antiviral drug discovery

SARS‐CoV‐2–host proteome interactions for antiviral drug discovery

Clinical significance of HEp-2 cell cytoplasmic patterns in anti-neutrophil cytoplasmic antibody associated vasculitis

The value of anti-rods and rings antibodies in patients with nonhepatitis virus infection

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