Clinical utility of anti‐cytosolic 5’‐nucleotidase 1A antibody in idiopathic inflammatory myopathies

Ikenaga, Chiseko; Findlay, Andrew; Goyal, Namita; Robinson, Sarah; Cauchi, Jonathan; Hussain, Yessar; Wang, Leo H.; Kershen, Joshua C.; Beson, Brent; Wallendorf, Michael; Bucelli, Robert C.; Mozaffar, Tahseen; Pestronk, Alan; Weihl, Conrad C.

doi:10.1002/acn3.51294

Cited by 19 publications

(36 citation statements)

References 27 publications

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“…12,13 The presence of anti-NT5c1A autoantibodies has also been reported as a poor prognostic factor in some studies, 15,20 although in others, no correlation was seen between seropositivity and prognosis. 21,22 These studies suggest that IBM is a much more heterogeneous condition than has previously been considered. A larger study of IBM is important to identify distinct subgroups of IBM patients and the prognostic factors that may influence their clinical trajectory.…”

Section: Introductionmentioning

confidence: 87%

Clinical heterogeneity based on race and sex within a large cohort of inclusion body myositis patients

Michelle

Pinal‐Fernandez

Casal-Domínguez

et al. 2022

Preprint

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Background and Objectives: Sporadic inclusion body myositis (IBM) is the most common acquired myopathy in individuals over age 50. The disorder is slowly progressive and while many therapies have been investigated, response has generally been poor. Clinical heterogeneity may influence treatment responsiveness; however, data regarding heterogeneity in IBM is limited and often conflicting. We aim to identify clinically distinct subgroups within a large IBM cohort, as well as prognostic factors for disease progression. Methods: Clinical, histologic, radiologic, and electrophysiologic data were analyzed for all patients with IBM and other forms of myositis enrolled in a longitudinal cohort from The Johns Hopkins Myositis Center from 2003-2018. Univariate, multivariate, and graphical analyses were used to identify prognostic factors in IBM patients. Results: Among the 335 IBM patients meeting inclusion criteria, 64% were male with an average age of disease onset of 58.7 years and a delay to diagnosis of 5.2 years. Initial misdiagnosis (52%) and immunosuppressant treatment (42%) were common. Less than half (43%) of muscle biopsies demonstrated all three pathologic hallmarks: endomysial inflammation, mononuclear cell invasion, and rimmed vacuoles. Black patients had significantly weaker arm abductors, hip flexors, and knee flexors compared to non-Black patients but were less likely to develop dysphagia. Female patients had stronger finger flexors and knee extensors compared to their male counterparts but were more likely to develop dysphagia. A significant number (20%) of patients had an age of onset less than 50 years. This group of younger patients was weaker at their first visit; however, this may be accounted for by a longer disease duration at first visit. Discussion: Although IBM has long been considered a disorder predominately of older, White men, female, and non-White patients comprise a significant proportion of the IBM population. Our study demonstrates that female and Black patients have distinct clinical phenotypes within the overarching IBM clinical phenotype.

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Section: Introductionmentioning

confidence: 87%

Clinical heterogeneity based on race and sex within a large cohort of inclusion body myositis patients

Michelle

Pinal‐Fernandez

Casal-Domínguez

et al. 2022

Preprint

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“…Creatinine Kinase (CK) levels are classically only mildly elevated (or normal) in IBM but can be a useful tool in formulating the diagnosis. There appears to be no relationship noted thus far in seropositive IBM patients and CK levels (25,27,30,32,36,37). Interestingly, in one study, CK levels were found to be significantly lower in seropositive patients diagnosed with inflammatory myopathies other than IBM (30).…”

Section: Anti-cn1a Antibody and Clinical Phenotype Or Other Disease F...mentioning

confidence: 92%

“…The sensitivity of this assay has varied from 35.5% to 66.7% (Table I) (24,29). The Washington University Neuromuscular Laboratory have achieved sensitivities varying between 63.9% to 72% using a technique involving western blotting followed by a confirmatory whole recombinant cN1A polypeptide ELISA (23,30). Herbert and Pruijn described early pilot work comparing the peptide ELI-SA with a whole recombinant cN1A ELISA in 55 IBM patients (28).…”

Section: Anti-cn1a Antibody Detectionmentioning

confidence: 99%

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Diagnostic and prognostic value of anti-cN1A antibodies in inclusion body myositis

Salam

Dimachkie

Hanna

et al. 2022

Clinical and Experimental Rheumatology

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Inclusion body myositis (IBM) is an acquired idiopathic inflammatory myopathy more commonly seen in individuals aged above 50. Unlike other idiopathic inflammatory myopathies, there is no response to immunosuppression/immunomodulation. The lack of response to such therapies led the focus away from considering IBM as a purely immunemediated condition. However, the discovery of antibodies against cytosolic 5́-nucleotidase 1A (cN1A) in patients with IBM has reinvigorated interest in autoimmunity as a key role in its pathogenesis. Over the last decade different methods have been developed to detect anti-cN1A antibodies. There has been an interest in whether these assays can be utilised in the diagnosis of IBM. Furthermore, there has been focus on whether anti-cN1A antibodies can be used to prognosticate and predict the clinical phenotype in IBM. Anti-cN1A antibodies appear to have a high specificity and moderate sensitivity for IBM. There have been some exploratory clinicopathological associations described in seropositive IBM patients, but sample sizes in most studies have been small so far. Antibody testing is yet to be standardised; which somewhat limits our ability to draw robust conclusions from current investigations. In this article we review the literature on anti-cN1A antibodies and discuss whether they have a role in clinical practice.

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“…Myopathy with onset in adulthood is extensively heterogeneous with a low likelihood of obtaining any genetic diagnosis; therefore, isolated myopathy on its own would not suggest a high likelihood of identifying VCP-MSP. However, myopathy is the most common presentation of VCP-MSP and it is possible that some cases of VCP-MSP are misdiagnosed as sporadic inclusion body myositis based on reactivity to NT5C1A antibodies [ 118 ]. Early-onset FTD is very rare and may portend a higher likelihood of identifying a causative gene mutation.…”

Section: Genetic Diagnosis Of Vcp-mspmentioning

confidence: 99%

Multisystem Proteinopathy Due to VCP Mutations: A Review of Clinical Heterogeneity and Genetic Diagnosis

Pfeffer

Lee

Pontifex

et al. 2022

Genes

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In this work, we review clinical features and genetic diagnosis of diseases caused by mutations in the gene encoding valosin-containing protein (VCP/p97), the functionally diverse AAA-ATPase. VCP is crucial to a multitude of cellular functions including protein quality control, stress granule formation and clearance, and genomic integrity functions, among others. Pathogenic mutations in VCP cause multisystem proteinopathy (VCP-MSP), an autosomal dominant, adult-onset disorder causing dysfunction in several tissue types. It can result in complex neurodegenerative conditions including inclusion body myopathy, frontotemporal dementia, amyotrophic lateral sclerosis, or combinations of these. There is also an association with other neurodegenerative phenotypes such as Alzheimer-type dementia and Parkinsonism. Non-neurological presentations include Paget disease of bone and may also include cardiac dysfunction. We provide a detailed discussion of genotype-phenotype correlations, recommendations for genetic diagnosis, and genetic counselling implications of VCP-MSP.

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Clinical utility of anti‐cytosolic 5’‐nucleotidase 1A antibody in idiopathic inflammatory myopathies

Cited by 19 publications

References 27 publications

Clinical heterogeneity based on race and sex within a large cohort of inclusion body myositis patients

Clinical heterogeneity based on race and sex within a large cohort of inclusion body myositis patients

Diagnostic and prognostic value of anti-cN1A antibodies in inclusion body myositis

Multisystem Proteinopathy Due to VCP Mutations: A Review of Clinical Heterogeneity and Genetic Diagnosis

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