Rapid reduction of viruria and stabilization of allograft function by fusidic acid in a renal transplant recipient with JC virus-associated nephropathy

Chan, Jasper Fuk‐Woo; Kam-Man, Maggie; Chan, Gavin Shueng-wai; Chan, G. C. F.; Choi, Garnet Kwan-Yue; Chan, Konan; Cheng, Vincent Chi-Chung; Chan, Kwok–Wah; Choy, Bo-Ying; Yuen, Kwok‐Yung

doi:10.1007/s15010-015-0721-x

Cited by 12 publications

(7 citation statements)

References 18 publications

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“…Indeed, kidney transplant patients are at risk of premature allograft failure (Castro et al, ; Funahashi et al, ). At risk patients can be identified before significant functional impairment of the renal allograft occurs (Castro et al, ; Chan et al, ; Funahashi et al, ; Querido et al, ; Saundh, Baker, Harris, & Hale, ). Our innovative ELISA with JCPyV VP1 mimotopes will be useful to study multiple sclerosis (MS) affected patients treated with monoclonal antibodies (mab), such as the natalizumab (Reuwer, Heron, van der Dussen, Schneider‐Hohendorf, & Murk, ).…”

Section: Discussionmentioning

confidence: 99%

Serum IgG antibodies from healthy subjects up to 100 years old react to JC polyomavirus

Bononi

Mazzoni

Pietrobon

et al. 2018

Journal Cellular Physiology

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JC polyomavirus (JCPyV) was identified in 1971 in the brain tissue of a patient (J.C.) affected by the progressive multifocal leukoencephalopathy (PML). JCPyV encodes for the oncoproteins large T antigen (Tag) and small t-antigen (tag). These oncoproteins are responsible of the cell transformation and tumorigenesis in experimental animals. JCPyV is ubiquitous in human populations. After the primary infection, which is usually asymptomatic, JCPyV remains lifelong in the host in a latent phase. Its reactivation may occur in heathy subjects and immunocompromised patients. Upon reactivation, JCPyV could reach (i) the CNS inducing the PML, (ii) the kidney of transplant patients causing the organ rejection. Association between JCPyV, which is a small DNA tumor virus, and gliomas and colorectal carcinomas has been published. In the present investigation, we report on a new indirect ELISA with two specific synthetic peptides mimicking JCPyV VP1 immunogenic epitopes to detect specific serum IgG antibodies against JCPyV. Serum samples of healthy subjects (n = 355) ranging 2-100 years old, were analyzed by this new indirect ELISA. The linear peptides VP1 K and VP1 N resemble the natural JCPyV VP1 capsidic epitopes constituting a docking site for serum antibodies. Data from this innovative immunologic assay indicate that the overall prevalence of JCPyV-VP1 antibodies in healthy subjects is at 39%. The innovative indirect ELISA with JCPyV VP1 mimotopes seems to be a useful method to detect specific IgG antibodies against this virus, without cross-reactivity with the closely related SV40 and BKPyV polyomaviruses.

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Section: Discussionmentioning

confidence: 99%

Serum IgG antibodies from healthy subjects up to 100 years old react to JC polyomavirus

Bononi

Mazzoni

Pietrobon

et al. 2018

Journal Cellular Physiology

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“…Categories of antibiotics with antiviral potential include macrolides (e.g., azithromycin, which demonstrated activity against SARS-CoV-2), tetracyclines (tetracycline, doxycycline, minocycline, which have been proposed in the treatment of COVID-19), fluoroquinolones (e.g., ciprofloxacin, levofloxacin, ofloxacin, which have shown efficacy against polyomavirus BK and influenza virus), aminoglycosides (e.g., on Japanese encephalitis and influenza A virus infection), chloramphenicol (e.g., on human Herpesviridae family), Colistin (polymyxin E, for example on mycobacteriophage D29 infection),and fusidic acid (e.g., on human immunodeficiency virus and John Cunningham virus infection) [61][62][63][64][65][66][67][68][69][70].…”

Section: Antibiotics and Other Antimicrobialsmentioning

confidence: 99%

A Panel of Broad-Spectrum Antivirals in Topical Ophthalmic Medications from the Drug Repurposing Approach during and after the Coronavirus Disease 2019 Era

Napoli

Mangoni

Gentile

et al. 2020

JCM

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The coronavirus disease 2019 (COVID-19) represents a global concern of public health caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Its clinical manifestations are characterized by a heterogeneous group of symptoms and pictures (ranging from asymptomatic to lethal courses). The prevalence of conjunctivitis in patients with COVID-19 is at present controversial. Although it has been reported that only 0.9% developed signs of conjunctivitis, other report indicates that up to 31.6% of hospitalized patients had conjunctivitis. Considering the widespread use of topical ophthalmic medications (e.g., eye drops) by the general population, for various reasons (e.g., artificial tears, anti-glaucoma medications, topical antibiotics, etc.), the existence of their side effects as antiviral action should be investigated in-depth because it could possibly explain the aforementioned controversial data and represent a potential antiviral treatment for SARS-CoV-2 replication/diffusion on the ocular surface. Here, we discuss and elucidate the antiviral side effect of many eye drops and ophthalmic ointments commonly used for others purposes, thus showing that these secondary effects (not to be confused with the ‘adverse effects’) might be of primary importance in a number of viral infections (e.g., those for which there is no validated treatment protocol), according to a drug repurposing approach. Some active ingredients or excipients described here have activity against other types of viruses, thus suggesting potential broad-spectrum applications.

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“…Fusidic acid, commonly used in Denmark for treatment of staphylococcal infections, has possible in vitro e cacy against JCV with a single case report describing effect against JCV associated nephropathy (9,10). In standard dosage, fusidic acid has relative low CSF penetration, but better into brain tissue (11)(12)(13).…”

Section: Resultsmentioning

confidence: 99%

Fatal JC-virus Granular Cerebellar Neuronopathy associated with Autoimmune Lymphoproliferative Syndrome and Common Variable Immunodeficiency

Helweg‐Larsen

Rasmussen

Rosenstierne

et al. 2020

Preprint

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Background: JC-virus (JCV) associated granular cerebellar neuronopathy (JCV-GCN), which causes severe ataxia, is a rare complication of severe immunodeficiency and caused by a variant of JCV with a VP1-deletion. JCV-GCN has not yet been reported in patients with autoimmune lymphoproliferative syndrome (ALPS-FAS). We report a 34-year old woman with autoimmune lymphoproliferative syndrome (ALPS-FAS) and common variable immunodeficiency (CVID) who developed JCV-GCN which progressed to fatal progressive multifocal leukoencephalopathy (PML).Methods: Extensive longitudinal virologic, genetic and immunologic characterisation by JCV CSF quantification and sequencing, peripheral blood flowcytometry and exome sequencing. Results: A diagnosis of JCV-GCN was established by findings of severe cerebellar vermis atrophy on MRI and a JCV variant with a VP1-deletion (JCV-VP1) in CSF. During a period of 18 months, at which treatment with high dose immunoglobulin, cidofovir, mirtazapine and high dose fucidic acid were given, cerebellar ataxia was relatively stable. In CSF a mixture of predominantly JCV-VP1 with only low levels of wildtype JCV was found. However, classic PML ensued, with rising JCV- CSF levels and a complete change to JCV-wildtype quasi species without JCV-VP1. Immunological findings were unusual, with disappearance of the original ALPS-FAS phenotype. Trio-exome sequencing identified a heterozygote de novo variant of unknown significance in RAG1. FAS mutations were not detected in the patient or in the parents, suggesting that her previously diagnosed ALPS-FAS-FAS was caused by somatic mosaicism. At the progression to PML, increased expression of T-cell PD-1 was demonstrated, suggesting T-cell exhaustion. Treatment with pembrolizumab, an inhibitor of PD-1, was attempted but followed by rapid and fatal PML progression. Conclusion: JCV-GCN may complicate ALPS and may progress to PML. In JCV-GCN, wild-type and JCV-VP-1 can co-exist in CSF. Quantification and sequencing of JCV in CSF is helpful to characterize and monitor disease and treatment. Progression of disease may be associated with development of T-cell exhaustion, but the benefit PD-1 inhibitor treatment is uncertain.

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Rapid reduction of viruria and stabilization of allograft function by fusidic acid in a renal transplant recipient with JC virus-associated nephropathy

Cited by 12 publications

References 18 publications

Serum IgG antibodies from healthy subjects up to 100 years old react to JC polyomavirus

Serum IgG antibodies from healthy subjects up to 100 years old react to JC polyomavirus

A Panel of Broad-Spectrum Antivirals in Topical Ophthalmic Medications from the Drug Repurposing Approach during and after the Coronavirus Disease 2019 Era

Fatal JC-virus Granular Cerebellar Neuronopathy associated with Autoimmune Lymphoproliferative Syndrome and Common Variable Immunodeficiency

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