Progressive multifocal leukoencephalopathy in individuals with minimal or occult immunosuppression

Gheuens, Sarah; Pierone, Gerald; Peeters, Patrick; Koralnik, Igor J.

doi:10.1136/jnnp.2009.187666

Cited by 170 publications

(145 citation statements)

References 40 publications

(25 reference statements)

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“…JCV is a ubiquitous virus that infects between 60 and 80% of the population worldwide. Under circumstances of immunocompromise and especially impaired CD4 + T cell function such as late-stage HIV infection, hematological malignancies, organ transplantation, but also in clinically inconspicuous idiopathic CD4 + lymphopenia (13)(14)(15), JCV is able to cause an opportunistic infection of the brain called progressive multifocal leukoencephalopathy (PML) (13,16,17). Because PML often runs a fatal course, it is an important medical concern.…”

Section: Irus-specific Cd4mentioning

confidence: 99%

TCR Bias and HLA Cross-Restriction Are Strategies of Human Brain-Infiltrating JC Virus-Specific CD4+ T Cells during Viral Infection

Yousef

Planas

Chakroun

et al. 2012

The Journal of Immunology

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Virus-specific CD4+ T cells play a central role in control of viral pathogens including JC polyoma virus (JCV) infection. JCV is a ubiquitous small DNA virus that leads to persistent infection of humans with no clinical consequences. However, under circumstances of immunocompromise, it is able to cause an opportunistic and often fatal infection of the brain called progressive multifocal leukoencephalopathy (PML). PML has emerged as a serious adverse event in multiple sclerosis patients treated with the anti–VLA-4 mAb natalizumab, which selectively inhibits cell migration across the blood–brain barrier and the gut’s vascular endothelium thus compromising immune surveillance in the CNS and gut. In a multiple sclerosis patient who developed PML under natalizumab treatment and a vigorous immune response against JCV after Ab washout, we had the unique opportunity to characterize in detail JCV-specific CD4+ T cell clones from the infected tissue during acute viral infection. The in-depth analysis of 14 brain-infiltrating, JCV-specific CD4+ T cell clones demonstrated that these cells use an unexpectedly broad spectrum of different strategies to mount an efficient JCV-specific immune response including TCR bias, HLA cross-restriction that increases avidity and influences in vivo expansion, and a combination of Th1 and Th1-2 functional phenotypes. The level of combinatorial diversity in TCR– and HLA–peptide interactions used by brain-infiltrating, JCV-specific CD4+ T cells has not, to our knowledge, been reported before in humans for other viral infections and confirms the exceptional plasticity that characterizes virus-specific immune responses.

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Section: Irus-specific Cd4mentioning

confidence: 99%

TCR Bias and HLA Cross-Restriction Are Strategies of Human Brain-Infiltrating JC Virus-Specific CD4+ T Cells during Viral Infection

Yousef

Planas

Chakroun

et al. 2012

The Journal of Immunology

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“…Specifically among patients with hepatic cirrhosis and portal hypertension, hypersplenism was often observed and may result in leukopenia, lymphopenia, or CD4+ lymphocytopenia due to splenic sequestration. Even in patients with cirrhosis but no evidence of decreased leukocyte counts, immune dysfunction in the form of abnormal cytokine production, vascular disturbances, and altered cellular immune responses may be adequate for the development of PML [1].…”

Section: Discussionmentioning

confidence: 99%

An Unusual Case of Progressive Multifocal Leukoencephalopathy in a Patient with Non-traditional Risk Factors

Je¹,

Zeiger²,

Sotirchos³

et al. 2015

J Neurol Disord

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Case ReportMr. A is a 52 year old man from Qatar with a past medical history of hypertension, diabetes mellitus type 2, hyperlipidemia, diverticulitis status post hemicolectomy, and cervical stenosis of C5-7 who began experiencing intermittent headaches, episodes of slurred speech, and decreased appetite from April to October 2014. In November 2014, he developed progressive weakness of his right lower extremity over three days, to the extent that he was unable to control his right lower extremity or walk properly. The weakness was associated with intermittent leg pain as well as numbness in both feet. He had no associated bowel or bladder symptoms. He presented to the emergency department of a local institution where an MRI of the brain demonstrated focal atrophy of the left post central and adjacent superior frontal gyri at the vertex with mild white matter T2 hyperintensity. His symptoms persisted and he was transferred to a higher level of care for further evaluation. During that admission he developed he developed new onset right upper extremity weakness in addition to his right lower extremity weakness. The following day, he experienced a focal motor seizure of the right upper and lower extremities. Phenytoin was prescribed and after he had a second seizure and levetiracetam was later added. Repeat MRI of the brain with and without contrast showed a non-enhancing T2 hyperintense lesion involving the left posterior frontal and parietal preand post-central gyri without significant mass effect. Unfortunately, the patient experienced multiple recurrent focal seizures that were resistant to multiple anti-epileptics and was intubated due to declining level of consciousness. A third MRI of the brain showed increased size of the left frontoparietal lesion and expansion into the occipital cortical and subcortical regions, with mild increase in mass effect, and intralesional dark foci on susceptibility weighted imaging concerning for petechial hemorrhage. Viral and bacterial cultures from the patient's cerebrospinal fluid (CSF) showed no growth. The patient was then transferred to our institution for further diagnostic evaluation.Shortly after arrival, the patient underwent repeat lumbar puncture. CSF analysis was notable for positive JC virus polymerase chain reaction. To make a more definitive diagnosis, brain biopsy AbstractProgressive multifocal leukoencephalopathy (PML) is a frequently fatal demyelinating condition of the central nervous system in which reactivation of the human polyomavirus JC (JCV) leads to lytic infection of oligodendrocytes. JCV reactivation typically occurs in the setting of profound impairment of cellular immunity seen in conditions such as human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS), hematologic malignancies, autoimmune diseases, and treatment with immunosuppressive medications. However, an emerging body of literature suggests that minimal or occult immunosuppression may be sufficient for the development of PML in certain cases. We report the ...

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“…Of a total of 38 cases, 7 (18.4%) had hepatic cirrhosis, 5 (13.2%) had renal failure, 2 (5.2%) were pregnant women, 2 (5.2%) had concomitant dementia, 1 (2.6%) had dermatomyositis and 22 (57.9%) had no specific underlying diagnosis. The outcome was fatal in 27/38 (71.1%) cases within 1.5-120 months (median 8 months) from onset of symptoms, and 3/4 cases who harbored JCV-specific T cells in their peripheral blood had inactive disease with stable neurological deficits after 6-26 months of follow-up [9].…”

Section: Discussionmentioning

confidence: 99%

Progressive multifocal leukoencephalopathy, a possible complication in a patient with bladder cancer

Latifyan¹,

Sideris²,

Papaleo³

et al. 2015

Clin Case Rep Rev

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Progressive multifocal leukoencephalopathy in individuals with minimal or occult immunosuppression

Cited by 170 publications

References 40 publications

TCR Bias and HLA Cross-Restriction Are Strategies of Human Brain-Infiltrating JC Virus-Specific CD4+ T Cells during Viral Infection

TCR Bias and HLA Cross-Restriction Are Strategies of Human Brain-Infiltrating JC Virus-Specific CD4+ T Cells during Viral Infection

An Unusual Case of Progressive Multifocal Leukoencephalopathy in a Patient with Non-traditional Risk Factors

Progressive multifocal leukoencephalopathy, a possible complication in a patient with bladder cancer

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