Alterations in <scp>Aquaporin‐4‐IgG</scp> Serostatus in 986 Patients: A Laboratory‐Based Longitudinal Analysis

Majed, Masoud; Valencia Sanchez, Cristina; Bennett, Jeffrey L.; Fryer, James; Mulligan, Martin D.; Redenbaugh, Vyankya; McKeon, Andrew; Mills, John R.; Wingerchuk, Dean M.; Lennon, Vanda A.; Weinshenker, Brian; Chen, John J.; Flanagan, Eoin P.; Pittock, Sean J.; Kunchok, Amy

doi:10.1002/ana.26722

Cited by 13 publications

(5 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, some patients may become at least temporarily antibody-negative with B-cell-directed therapies or anti-IL-6-R therapy over time. Recently one large study (933 initially AQP4-gG positive patients) demonstrated that seroreversion is rare (11%), occurs predominantly in younger patients (age < 20 years) and in patients with initially low AQP4-IgG titers and is often transient [ 139 ]. Patients who serorevert are still considered AQP4-IgG-positive NMOSD cases, as in the RIN-1 trial.…”

Section: Treatment Of Nmosd: General Aspects and Outcome Measuresmentioning

confidence: 99%

Update on the diagnosis and treatment of neuromyelitis optica spectrum disorders (NMOSD) – revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part II: Attack therapy and long-term management

Kuempfel¹,

Giglhuber²,

Aktaş³

et al. 2023

J Neurol

View full text Add to dashboard Cite

This manuscript presents practical recommendations for managing acute attacks and implementing preventive immunotherapies for neuromyelitis optica spectrum disorders (NMOSD), a rare autoimmune disease that causes severe inflammation in the central nervous system (CNS), primarily affecting the optic nerves, spinal cord, and brainstem. The pillars of NMOSD therapy are attack treatment and attack prevention to minimize the accrual of neurological disability. Aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) are a diagnostic marker of the disease and play a significant role in its pathogenicity. Recent advances in understanding NMOSD have led to the development of new therapies and the completion of randomized controlled trials. Four preventive immunotherapies have now been approved for AQP4-IgG-positive NMOSD in many regions of the world: eculizumab, ravulizumab - most recently-, inebilizumab, and satralizumab. These new drugs may potentially substitute rituximab and classical immunosuppressive therapies, which were as yet the mainstay of treatment for both, AQP4-IgG-positive and -negative NMOSD. Here, the Neuromyelitis Optica Study Group (NEMOS) provides an overview of the current state of knowledge on NMOSD treatments and offers statements and practical recommendations on the therapy management and use of all available immunotherapies for this disease. Unmet needs and AQP4-IgG-negative NMOSD are also discussed. The recommendations were developed using a Delphi-based consensus method among the core author group and at expert discussions at NEMOS meetings.

show abstract

Section: Treatment Of Nmosd: General Aspects and Outcome Measuresmentioning

confidence: 99%

Update on the diagnosis and treatment of neuromyelitis optica spectrum disorders (NMOSD) – revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part II: Attack therapy and long-term management

Kuempfel¹,

Giglhuber²,

Aktaş³

et al. 2023

J Neurol

View full text Add to dashboard Cite

show abstract

“…Indeed, over 3.7 years, one third of the treated AQP4+ NMO patients seroreverts to AQP4 negative. 34,35…”

Section: Discussionmentioning

confidence: 99%

Human stem cell derived neurons and astrocytes to detect novel auto-reactive IgG signature in immune-mediated neurological diseases

Mathias,

Perriot,

Jones

et al. 2024

Preprint

View full text Add to dashboard Cite

Up to 46% of patients with presumed autoimmune limbic encephalitis are seronegative for all currently known CNS antigens. We developed a cell-based assay (CBA) to screen for novel neural antibodies in serum and cerebrospinal fluid (CSF) using neurons and astrocytes derived from human induced pluripotent stem cells (hiPSC).In this study, hiPSC-derived neural cells seeded on 96-well plates (96-well CBA) were incubated with serum or CSF from 99 patients, including 42 with inflammatory neurological diseases (IND) and 57 with non-IND (NIND). The IND group included 11 patients with previously established neural antibodies, six with seronegative neuromyelitis optica spectrum disorder (NMOSD), 12 with suspected autoimmune encephalitis/paraneoplastic syndrome (AIE/PNS), and 13 with other IND (OIND). IgG bound to fixed CNS cells were detected using a combination of fluorescently-labelled antibodies. IgG-associated fluorescence intensity measures and microscopy observations were automated. IgG reactivity to neurons and astrocytes was further analyzed by flow cytometry. Peripheral blood mononuclear cells (PBMC) were used as CNS-irrelevant control target cells. Reactivity profile was defined as positive using a Robust regression and Outlier removal test with a false discovery rate at 10% following each individual readout.Using our 96-well CBA, we detected antibodies recognizing hiPSC-derived neural cells in 19/99 (19.2%) study patients. Antibodies bound specifically to astrocytes in nine cases, to neurons in eight cases and to both cell types in two cases. Microscopy single-cell analyses ascertained cellular distribution and binding specificity. Highlighting the significance of our novel 96-well CBA assay, the occurrence of CNS-specific antibody binding was more frequent in IND (15/42) than in NIND patients (4/57) (Fisher test,p=0.0005). Three of three patients with astrocyte-reactive (2 AQP4+ NMO, 1 GFAP astrocytopathy), and 3/4 with intracellular neuron-reactive antibodies (2 Hu+, 1 Ri+ AIE/PNS), as identified in validated diagnostic laboratories, were also positive with our CBA assay. Most interestingly, we showed antibody-reactivity in 2/6 seronegative NMOSD, 6/12 probable AIE/PNS, and 1/13 OIND. Flow cytometry using hiPSC-derived CNS cells or PBMC detected antibody binding in 13 versus 0 patients, respectively, establishing the specificity of the detected antibodies for neural tissue.Our unique hiPSC-based 96-well CBA allows for the screening of neuron-or astrocyte-reactive antibodies in patients with suspected immune-mediated neurological syndromes, and negative testing in established routine laboratories. Such a potent tool opens new perspectives in establishing early diagnosis of Ab-mediated diseases of the CNS.

show abstract

“…In patients with a strong diagnostic suspicion and a negative test result, repeat testing in specialized laboratories on stored samples obtained acutely is reasonable. Repeat testing over time (eg, after 1 to 2 years) may also be considered in highly suspected cases as seroconversion to positivity after an initially negative test result may occur in both diseases in a minority of patients 64 . Serum positivity for AQP4 IgG usually persists over time with minimal titer fluctuations, 64 which facilitates the diagnosis in patients evaluated years after disease onset.…”

Section: Diagnosismentioning

confidence: 99%

“…Repeat testing over time (eg, after 1 to 2 years) may also be considered in highly suspected cases as seroconversion to positivity after an initially negative test result may occur in both diseases in a minority of patients 64 . Serum positivity for AQP4 IgG usually persists over time with minimal titer fluctuations, 64 which facilitates the diagnosis in patients evaluated years after disease onset. Conversely, patients with MOG IgG may become seronegative over time, which may limit the diagnosis outside of the acute setting 55 .…”

Section: Diagnosismentioning

confidence: 99%

NMOSD and MOGAD

Sechi

2024

CONTINUUM: Lifelong Learning in Neurology

View full text Add to dashboard Cite

OBJECTIVE This article reviews the clinical features, MRI characteristics, diagnosis, and treatment of aquaporin-4 antibody–positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) and myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD). The main differences between these disorders and multiple sclerosis (MS), the most common demyelinating disease of the central nervous system (CNS), are also highlighted. LATEST DEVELOPMENTS The past 20 years have seen important advances in understanding rare demyelinating CNS disorders associated with AQP4 IgG and myelin oligodendrocyte glycoprotein (MOG) IgG. The rapidly expanding repertoire of immunosuppressive agents approved for the treatment of AQP4-NMOSD and emerging as potentially beneficial in MOGAD mandates prompt recognition of these diseases. Most of the recent literature has focused on the identification of clinical and MRI features that help distinguish these diseases from each other and MS, simultaneously highlighting major diagnostic pitfalls that may lead to misdiagnosis. An awareness of the limitations of currently available assays for AQP4 IgG and MOG IgG detection is fundamental for identifying rare false antibody positivity and avoiding inappropriate treatments. For this purpose, diagnostic criteria have been created to help the clinician interpret antibody testing results and recognize the clinical and MRI phenotypes associated with AQP4-NMOSD and MOGAD. ESSENTIAL POINTS An awareness of the specific clinical and MRI features associated with AQP4-NMOSD and MOGAD and the limitations of currently available antibody testing assays is crucial for a correct diagnosis and differentiation from MS. The growing availability of effective treatment options will lead to personalized therapies and improved outcomes.

show abstract

Alterations in Aquaporin‐4‐IgG Serostatus in 986 Patients: A Laboratory‐Based Longitudinal Analysis

Cited by 13 publications

References 30 publications

Update on the diagnosis and treatment of neuromyelitis optica spectrum disorders (NMOSD) – revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part II: Attack therapy and long-term management

Update on the diagnosis and treatment of neuromyelitis optica spectrum disorders (NMOSD) – revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part II: Attack therapy and long-term management

Human stem cell derived neurons and astrocytes to detect novel auto-reactive IgG signature in immune-mediated neurological diseases

NMOSD and MOGAD

Contact Info

Product

Resources

About