Neutropenia in Patients With Multiple Sclerosis Treated With Alemtuzumab

Gaitán, María I.; Ysrraelit, María Célica; Correale, Jorge

doi:10.1001/jamaneurol.2017.1456

Cited by 26 publications

(22 citation statements)

References 7 publications

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“…In addition to thyroid disorders, nephropathy and idiopathic thrombocytopenic purpura, cases of haemolytic anaemia4 and autoimmune neutropenia16 have recently been reported. The current monitoring programme for emergence of AIDs following alemtuzumab treatment in Australia involves TFTs, full blood count (FBC), serum creatinine (Cr) and urinalysis with microscopy prior to treatment and then monthly FBC, Cr and urinalysis and three monthly TFTs until 48 months after the last infusion 17.…”

Section: Discussionmentioning

confidence: 99%

Acquired haemophilia A complicating alemtuzumab therapy for multiple sclerosis

McCaughan

Massey²,

Sutton

et al. 2017

BMJ Case Reports

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Alemtuzumab is a highly efficacious therapy used in the treatment of multiple sclerosis (MS), but uncoupling of T and B cell repopulation during immune reconstitution associates with an increasing range of secondary B cell-mediated autoimmune complications. A 34-year-old woman developed Graves' disease 11 months following an initial course of alemtuzumab treatment for MS. Nine months following the second treatment with alemtuzumab, the patient presented with spontaneous intramuscular and subcutaneous haemorrhage due to development of an inhibitory autoantibody to coagulation factor VIII. Acquired haemophilia A (AHA) is an extremely rare complication in patients treated with alemtuzumab. Treatment with rituximab may induce a rapid remission of AHA; however, the patient's high John Cunningham virus (JCV) antibody index and alemtuzumab-induced T cell lymphopenia may lead to an increased risk of progressive multifocal leucoencephalopathy, a potential complication which was unacceptable to the patient.

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Section: Discussionmentioning

confidence: 99%

Acquired haemophilia A complicating alemtuzumab therapy for multiple sclerosis

McCaughan

Massey²,

Sutton

et al. 2017

BMJ Case Reports

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“…The immunomodulatory antibodies Ocrelizumab [72], Ofatumumab [73], and Rituximab [74] target CD20 to deplete B cells, and all decrease neutrophil counts [75,76,77,78]. Alemtuzumab targets CD52 to deplete lymphocytes (B cells and T cells) [79], and impairs neutrophil function [80,81]. Natalizumab binds to the lymphocyte membrane integrin alpha-4 (α 4 ) and competitively inhibits its interaction with vascular cell adhesion molecule (VCAM)-1, expressed on endothelial cells, thereby interfering with lymphocyte migration [82,83,84].…”

Section: Immunomodulatory Antibodiesmentioning

confidence: 99%

The Emerging Role of Neutrophil Granulocytes in Multiple Sclerosis

Woodberry

Bouffler

Wilson

et al. 2018

JCM

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Multiple sclerosis (MS) is a demyelinating disease of the central nervous system with a strong autoimmune, neurodegenerative, and neuroinflammatory component. Most of the common disease modifying treatments (DMTs) for MS modulate the immune response targeting disease associated T and B cells and while none directly target neutrophils, several DMTs do impact their abundance or function. The role of neutrophils in MS remains unknown and research is ongoing to better understand the phenotype, function, and contribution of neutrophils to both disease onset and stage of disease. Here we summarize the current state of knowledge of neutrophils and their function in MS, including in the rodent based MS model, and we discuss the potential effects of current treatments on these functions. We propose that neutrophils are likely to participate in MS pathogenesis and their abundance and function warrant monitoring in MS.

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“…The immune-suppressive dimethylfumarate impairs neutrophil function in vitro and in mouse models [ 166 ]. Concerning immunomodulatory antibodies, natalizumab has no effect on neutrophil function or number, whereas alemtuzumab induces neutrophil depletion and impairs neutrophil function [ 167 , 168 ].…”

Section: Discussionmentioning

confidence: 99%

Neutrophils: Underestimated Players in the Pathogenesis of Multiple Sclerosis (MS)

Bondt

Hellings

Opdenakker

et al. 2020

IJMS

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Neutrophils are the most abundant circulating and first-responding innate myeloid cells and have so far been underestimated in the context of multiple sclerosis (MS). MS is the most frequent, immune-mediated, inflammatory disease of the central nervous system. MS is treatable but not curable and its cause(s) and pathogenesis remain elusive. The involvement of neutrophils in MS pathogenesis has been suggested by the use of preclinical animal disease models, as well as on the basis of patient sample analysis. In this review, we provide an overview of the possible mechanisms and functions by which neutrophils may contribute to the development and pathology of MS. Neutrophils display a broad variety of effector functions enabling disease pathogenesis, including (1) the release of inflammatory mediators and enzymes, such as interleukin-1β, myeloperoxidase and various proteinases, (2) destruction and phagocytosis of myelin (as debris), (3) release of neutrophil extracellular traps, (4) production of reactive oxygen species, (5) breakdown of the blood–brain barrier and (6) generation and presentation of autoantigens. An important question relates to the issue of whether neutrophils exhibit a predominantly proinflammatory function or are also implicated in the resolution of chronic inflammatory responses in MS.

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Neutropenia in Patients With Multiple Sclerosis Treated With Alemtuzumab

Cited by 26 publications

References 7 publications

Acquired haemophilia A complicating alemtuzumab therapy for multiple sclerosis

Acquired haemophilia A complicating alemtuzumab therapy for multiple sclerosis

The Emerging Role of Neutrophil Granulocytes in Multiple Sclerosis

Neutrophils: Underestimated Players in the Pathogenesis of Multiple Sclerosis (MS)

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