PML risk stratification using anti-JCV antibody index and L-selectin

Schwab, Nicholas; Schneider‐Hohendorf, Tilman; Pignolet, Béatrice; Spadaro, Michela; Görlich, Dennis; Meinl, Ingrid; Windhagen, Susanne; Tackenberg, Björn; Breuer, Johanna; Cantó, Ester; Kümpfel, Tania; Hohlfeld, Reinhard; Siffrin, Volker; Luessi, Felix; Posevitz-Fejfar, Anita; Montalbán, Xavier; Meuth, Sven G.; Zipp, Frauke; Gold, Ralf; Pasquier, Renaud Du; Kleinschnitz, Christoph; Jacobi, Annett M.; Comabella, Manuel; Bertolotto, Antonio; Brassat, David; Wiendl, Heinz

doi:10.1177/1352458515607651

Cited by 60 publications

(39 citation statements)

References 28 publications

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“…For patients with MS, JCV serostatus is a known risk factor for natalizumab-induced PML; it is unknown whether JCV serostatus is an important risk factor for other vulnerable populations, such as those with hematologic malignancies. 17,18 When monoclonal antibodies were introduced in the treatment of MS, and as patients started to develop PML, immunosuppressive algorithms were constructed to stratify the risk potential for PML and consensus guidelines detailed the timing of periodic anti-JCV antibody testing. Biomarkers, such as the anti-JCV antibody index, are being investigated to identify MS patients at greatest risk of developing PML and to direct the use of immunomodulating therapy.…”

Section: Discussionmentioning

confidence: 99%

Progressive multifocal leukoencephalopathy and hematologic malignancies: a single cancer center retrospective review

Neil

DeAngelis

2017

Blood Advances

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Section: Discussionmentioning

confidence: 99%

Progressive multifocal leukoencephalopathy and hematologic malignancies: a single cancer center retrospective review

Neil

DeAngelis

2017

Blood Advances

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“…Classicaly, 3 risk factors have been established: anti-JCV antibody status, duration of treatment with natalizumab of > 2 years, and prior treatment with immunosuppressive therapies such as mitoxantrone. Currently, 2 novel independent approaches are being evaluated that have been proposed as additional risk stratification parameters: anti-JCV antibody titers and Lselectin (CD62L) expression levels [42][43][44]. While the association of PML and natalizumab is well established, a small number of cases have also been reported for patients treated with dimethylfumarate and fingolimod [45,46].…”

Section: Natalizumabmentioning

confidence: 99%

Neuroimmunotherapies Targeting T Cells: From Pathophysiology to Therapeutic Applications

Bittner

Wiendl

2016

Neurotherapeutics

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Therapeutic options for multiple sclerosis (MS) have significantly increased over the last few years. T lymphocytes are considered to play a central role in initiating and perpetuating the pathological immune response. Currently approved therapies for MS target T lymphocytes, either in an unspecific manner or directly by interference with specific Tcell pathways. While the concept of BT-cell-specific therapyî mplies specificity and selectivity, currently approved approaches come from a general shaping of the immune system towards anti-inflammatory immune responses by non-T-cellselective immune suppression or immune modulation (e.g., interferons-immune modulation approach) to a depletion of immune cell populations involving T cells (e.g., anti-CD52, alemtuzumab-immune selective depletion approach), or a selective inhibition of distinct molecular pathways in order to sequester leucocytes (e.g., natalizumab-leukocyte sequestration approach). This review will highlight the rationale and results of different T-cell-directed therapeutic approaches coming from basic animal experiments to clinical trials. We will first discuss the pathophysiological rationale for targeting T lymphocytes in MS leading to currently approved treatments acting on T lymphocytes. Furthermore, we will disuss previous promising concepts that have failed to show efficacy in clinical trials or were halted as a result of unexpected adverse events. Learning from the discrepancies between expectations and failures in practical outcomes helps to optimize future research approaches and clinical study designs. As our current view of MS pathogenesis and patient needs is rapidly evolving, novel therapeutic approaches targeting T lymphocytes will also be discussed, including specific molecular interventions such as cytokine-directed treatments or strategies enhancing immunoregulatory mechanisms. Based on clinical experience and novel pathophysiological approaches, T-cell-based strategies will remain a pillarstone of MS therapy.

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“…Neuere Arbeiten beschreiben einen erhöhten JCV-Antikörpertiter im Serum (OD(optical density)-Werte im entsprechenden ELI-SA mit Grenzwerten von > 0,9 bzw. > 1,5, hier bezeichnet als "Index") sowie eine reduzierte Expression des Adhäsi-onsmoleküls CD62L auf CD4-T-Zellen als mögliche Prädiktoren für eine PMLEntwicklung im weiteren Verlauf [67,75,76]. Der Nachweis von lipidspezifischem, oligoklonalem IgM im Liquor wurde zudem als negativer Prädiktor für eine zukünftige PML beschrieben [85].…”

Section: Natalizumab (Tysabri ® )unclassified

“…Die Wahrscheinlichkeit einer Serokonversion unter NAT liegt bei ca. 10 % pro Jahr, also etwas höher als in der Allgemeinbevölkerung oder MS-Population ohne Natalizumab (2-3 %/Jahr) [67,76].…”

Section: Praktisches Vorgehenunclassified

Monitoring von Blutparametern unter verlaufsmodifizierender MS-Therapie

et al. 2016

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With the approval of various substances for the immunotherapy of multiple sclerosis (MS), treatment possibilities have improved significantly over the last few years. Indeed, the choice of individually tailored preparations and treatment monitoring for the treating doctor is becoming increasingly more complex. This is particularly applicable for monitoring for a treatment-induced compromise of the immune system. The following article by members of the German Multiple Sclerosis Skills Network (KKNMS) and the task force "Provision Structures and Therapeutics" summarizes the practical recommendations for approved immunotherapy for mild to moderate and for (highly) active courses of MS. The focus is on elucidating the substance-specific relevance of particular laboratory parameters with regard to the mechanism of action and the side effects profile. To enable appropriate action to be taken in clinical practice, any blood work changes that can be expected, in addition to any undesirable laboratory findings and their causes and relevance, should be elucidated.

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PML risk stratification using anti-JCV antibody index and L-selectin

Abstract: Both JCV index and CD62L have merit for risk stratification and share a potential biological relationship with implications for general PML etiology. A risk algorithm incorporating both biomarkers could strongly reduce PML incidence.

Cited by 60 publications

References 28 publications

Progressive multifocal leukoencephalopathy and hematologic malignancies: a single cancer center retrospective review

Progressive multifocal leukoencephalopathy and hematologic malignancies: a single cancer center retrospective review

Neuroimmunotherapies Targeting T Cells: From Pathophysiology to Therapeutic Applications

Monitoring von Blutparametern unter verlaufsmodifizierender MS-Therapie

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