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Background: Inclusion body myositis (IBM) is the most common sporadic idiopathic inflammatory myopathy (IIM) in individuals over 50 years, marked by asymmetric muscle weakness, progressive disability, and dysphagia in 60% of cases, which worsens the prognosis. Unlike other IIMs, IBM does not respond to immunosuppressive therapy. The discovery of the anti-cytosolic 5’-nucleotidase 1A (anti-cN1A) antibody has raised the possibility of an autoimmune origin for IBM, although this antibody is also present in other autoimmune diseases, and its exact role in these conditions is still uncertain.
Objectives: This study aimed to describe a cohort of patients with positive anti-cN1A results, focusing on the reasons for requesting the antibody and the final diagnoses, based on EULAR/ACR 2017 criteria. A secondary objective was to develop a clinical management algorithm for interpreting and managing positive anti-cN1A results.
Methods: Our cohort was derived from the registry of patients with positive anti-cN1A titers, determined by ELISA in the immunology laboratory of our center. A retrospective analysis evaluated clinical manifestations, laboratory findings, and histopathological results, including muscle biopsies. Patients were categorized into five groups based on clinical, laboratory, and electromyographic findings:
IBM diagnosed based on typical clinical and histological features.
Connective tissue diseases without myopathy.
Myopathy with clinical presentations or antibodies suggesting other immune-mediated myopathies.
Myopathy without other features suggesting IIM or IBM.
Oligosymptomatic patients (minimal muscle damage markers or mild weakness).
Continuous variables were summarized using means and interquartile ranges (IQR), while categorical variables were reported as absolute frequencies and percentages.
Results: The cohort consisted of 31 patients, primarily women (71%), with a median age of 58 years (IQR 48–71). Nine patients (29%) were diagnosed with IBM, mostly women (66.6%) with a median age of 66 years (IQR 59–73). Clinical features included proximal muscle weakness (77%), distal weakness (22%), and dysphagia (55.5%). Eight (88%) had muscle biopsy findings compatible with IBM. Eight patients (25.8%) were diagnosed with connective tissue diseases, including systemic lupus erythematosus (3), Sjögren’s syndrome (2), eosinophilic fasciitis (2), and systemic sclerosis (1). This group had a median age of 48 years (IQR 42–52). Proximal muscle weakness was observed in five patients (62.5%), but none had myopathy evidence on lab tests or electromyography. Muscle biopsies were performed in four, with one showing nonspecific polymyositis. Eight patients (25.8%) were diagnosed with other immune-mediated myopathies, such as dermatomyositis (3), antisynthetase syndrome (2), and immune checkpoint inhibitor-associated myopathy (2). This group had a median age of 58 years (IQR 54–65), with cutaneous involvement, interstitial lung disease, and prior immunotherapy exposure. Muscle biopsy was done in five cases (71.4%), with no findings suggesting IBM. Three patients (9.7%) presented with only proximal muscle weakness. The median age was 78 years (IQR 40–80), and none showed myopathy in lab tests or electromyography. Muscle biopsies revealed myopathy in one patient diagnosed with limb-girdle muscular dystrophy and denervation in another, leading to a diagnosis of distal radiculopathy. Three patients (9.7%) had persistent myalgias without muscle weakness, with a mean age of 42 years (IQR 29–63). Muscle biopsy showed no abnormalities in two cases.
Conclusion: This study provided insights into the primary motivations for ordering anti-cN1A antibody testing at our center. Proximal muscle weakness was the main reason for testing, often without a phenotype suggesting IBM and with alternative diagnoses being more plausible. The high initial demand likely stemmed from the inclusion of anti-cN1A in a broader myopathy diagnostic panel. To address this, we implemented a protocol requiring approval from the Muscle Unit before testing. Anti-cN1A testing was also frequently ordered in patients with connective tissue diseases, even though positivity for anti-cN1A does not seem to increase the risk of developing IBM in these patients. In cases where a clear diagnosis of muscle weakness was not made, uncertainty led to invasive follow-up procedures and psychological stress for patients concerned about degenerative diseases. This highlights the importance of a structured approach in interpreting positive anti-cN1A results. Based on our experience, we recommend the following for a positive anti-cN1A result:
For patients with a classical IBM phenotype, muscle biopsy and specialized follow-up are recommended.
For patients with known connective tissue diseases and no signs of myopathy, invasive testing (electromyogram, muscle biopsy) is not recommended. Follow-up should focus on the underlying disease.
For patients with myopathy showing features or markers of other IIMs, muscle biopsy is recommended for diagnostic confirmation and disease-specific follow-up.
For patients with mild symptoms or no clear myopathy, we recommend reassuring the patient and educating them about alarm signs (worsening weakness, dysphagia). For male patients over 65 years with mild symptoms, an MRI of the forearm may help identify early muscle atrophy related to IBM, with muscle biopsy considered if findings are compelling.
REFERENCES: NIL.
Acknowledgements: NIL.
Disclosure of Interests: None declared.
© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (