Monoclonal Antibodies and Progressive Multifocal Leukoencephalopathy

Keene, Daniel; Legare, Carole; Taylor, Erik A.; Gallivan, Jim; Cawthorn, Gloria Mah; Vu, Duc

doi:10.1017/s0317167100012105

Cited by 59 publications

(32 citation statements)

References 58 publications

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“…The majority of these cases are due to the use of natalizumab (anti-␣4 integrin), which prevents T cell trafficking into the brain and is used for treatment of multiple sclerosis, and rituximab, which targets B cells (anti-CD20). However, cases have also been reported with alemtuzumab (anti-CD52), infliximab (anti-TNF), efalizumab (anti-CD11a), and ibritumomab (anti-CD20) (227). Immune compromise alone may not be sufficient to cause PML.…”

Section: Risk Factors In the Development Of Pmlmentioning

confidence: 99%

Molecular Biology, Epidemiology, and Pathogenesis of Progressive Multifocal Leukoencephalopathy, the JC Virus-Induced Demyelinating Disease of the Human Brain

et al. 2012

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SUMMARY Progressive multifocal leukoencephalopathy (PML) is a debilitating and frequently fatal central nervous system (CNS) demyelinating disease caused by JC virus (JCV), for which there is currently no effective treatment. Lytic infection of oligodendrocytes in the brain leads to their eventual destruction and progressive demyelination, resulting in multiple foci of lesions in the white matter of the brain. Before the mid-1980s, PML was a relatively rare disease, reported to occur primarily in those with underlying neoplastic conditions affecting immune function and, more rarely, in allograft recipients receiving immunosuppressive drugs. However, with the onset of the AIDS pandemic, the incidence of PML has increased dramatically. Approximately 3 to 5% of HIV-infected individuals will develop PML, which is classified as an AIDS-defining illness. In addition, the recent advent of humanized monoclonal antibody therapy for the treatment of autoimmune inflammatory diseases such as multiple sclerosis (MS) and Crohn's disease has also led to an increased risk of PML as a side effect of immunotherapy. Thus, the study of JCV and the elucidation of the underlying causes of PML are important and active areas of research that may lead to new insights into immune function and host antiviral defense, as well as to potential new therapies.

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Section: Risk Factors In the Development Of Pmlmentioning

confidence: 99%

Molecular Biology, Epidemiology, and Pathogenesis of Progressive Multifocal Leukoencephalopathy, the JC Virus-Induced Demyelinating Disease of the Human Brain

et al. 2012

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“…The primary infection by JC virus is probably engaging the tonsils and parapharyngeal lymph nodes and is disseminated by the tonsillar B lymphocytes to the kidney, spleen, lung, lymph node and bone marrow, where it is dormant until the development of an immunosuppressive state that permits JC virus mutation, reactivation, replication and invasion of the central nervous system 4 6 7. Serum antibodies against JC virus are detected in more than 50% of the adult population 4 6…”

Section: Discussionmentioning

confidence: 99%

“…Clinically, the disorder presents subacutely with cognitive impairment, motor symptoms, speech difficulties and symptoms of visual field deficits 2 6 7. Neurological signs and symptoms of PML depend on the location of the lesions in the central nervous system 8.…”

Section: Discussionmentioning

confidence: 99%

“…The disease does not usually involve the optic nerves or spinal cord 2. MRI demonstrates bilateral, asymmetric lesions, usually in the subcortical white matter, which are hypointense on T1-weighted images, and hyperintense on T2-weighted and FLAIR images 2 7. The lesions usually showed no gadolinium enhancement or oedema and are well demarcated 7.…”

Section: Discussionmentioning

confidence: 99%

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Progressive multifocal leukoencephalopathy during treatment with rituximab and CHOP chemotherapy in a patient with a diffuse large B-cell lymphoma

Sikkema¹,

Schuiling

Hoogendoorn

2013

BMJ Case Reports

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SUMMARYA 74-year-old woman with a diffuse large B-cell lymphoma was treated with rituximab and CHOP chemotherapy. After three cycles of chemotherapy she developed progressive symptoms of motor imbalance, fatigue, weight loss and impaired cognitive function, which was interpreted as toxicity of the CHOP chemotherapy. The sixth cycle CHOP chemotherapy was withheld and three additional cycles of rituximab were given. Two weeks later, neurological symptoms appeared, including abducens nerve palsy of her left eye, ataxia and hemiparesis of her right body. MRI of the brain revealed two hyperintense lesions on T2-weighted and fluid-attenuated inversion recovery images without oedema or gadolinium enhancement. A PCR on John Cunningham (JC) virus DNA in cerebrospinal fluid was negative, but subsequent brain biopsy diagnosed progressive multifocal leukoencephalopathy (PML). She rapidly deteriorated and died. Awareness of PML during immunosuppressive therapy can be lifesaving, since only immune reconstitution can prevent mortality in these patients. BACKGROUND

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“…Although the majority of the cases were seen in hematological malignancies with confounding effects of other immunosuppressants, there were 6 cases in patients with rheumatoid arthritis. The conclusion is that RTX may increase the risk of developing PML, but absolute risks are probably low [36]. …”

Section: Current Therapy For Anca-positive Rpgnmentioning

confidence: 99%

Treatment of Rapidly Progressive Glomerulonephritis in the Elderly

Appel¹,

Lau²

2018

Blood Purif

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As the population worldwide ages, the epidemic of kidney disease will also increase. Anti-neutrophil cytoplasmic antibodies (ANCA) positive rapidly progressive positive glomerulonephritis (RPGN) is the most common etiology for biopsied patients among the very elderly. Its pathological features and clinical course are well described, though there is still debate about the mechanism of injury involved in individual patients. From very ancient times, the cornerstone of treatment historically has been high-dose cyclophosphamide and a lengthy course of high-dose corticosteroids. Although this regimen has diminished the immediate mortality rate of RPGN, its intermediate and long-term adverse effects are not insignificant. Attempts to minimize toxicity and improve efficacy have been made through the years to allow physicians some options for therapy. Lower cumulative cyclophosphamide regimens, shorter corticosteroid courses, and the introduction of rituximab have modified the armamentarium for treatment of ANCA positive RPGN. As progress is made in understanding the molecular pathogenesis of this disease, new targets will be found for potential therapeutic attack. The complement system is an area of active interest for all glomerular diseases at this time. Indeed, animal studies and preliminary human studies suggest that targeting the complement system can ameliorate the course of ANCA-positive RPGN. Hopefully, as the population ages, we will see more and safer therapeutic options to treat this once rapidly fatal disease.

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Monoclonal Antibodies and Progressive Multifocal Leukoencephalopathy

Cited by 59 publications

References 58 publications

Molecular Biology, Epidemiology, and Pathogenesis of Progressive Multifocal Leukoencephalopathy, the JC Virus-Induced Demyelinating Disease of the Human Brain

Molecular Biology, Epidemiology, and Pathogenesis of Progressive Multifocal Leukoencephalopathy, the JC Virus-Induced Demyelinating Disease of the Human Brain

Progressive multifocal leukoencephalopathy during treatment with rituximab and CHOP chemotherapy in a patient with a diffuse large B-cell lymphoma

Treatment of Rapidly Progressive Glomerulonephritis in the Elderly

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