Antibodies Associated with Inclusion Body Myositis (IBM)
Anti-cytosolic 5'-nucleotidase 1A (anti-cN1A) antibodies are the primary antibodies associated with Inclusion Body Myositis (IBM). 1, 2
Anti-cN1A Antibodies in IBM
- Anti-cN1A (also known as anti-Mup44) antibodies represent the first identified serological biomarker specific for sporadic IBM 1
- These antibodies target cytosolic 5'-nucleotidase 1A protein and are found in approximately 33% of IBM patients 1
- High reactivity of anti-cN1A antibodies is 34% sensitive and 98% specific for IBM diagnosis 2
- Moderate reactivity of anti-cN1A antibodies is 70% sensitive and 92% specific for IBM diagnosis 2
Diagnostic Value and Limitations
- Anti-cN1A antibodies accumulate in perinuclear regions and rimmed vacuoles in IBM muscle, localizing to areas of myonuclear degeneration 2
- These antibodies may provide a link between IBM's dual processes of autoimmunity and myodegeneration 2
- While highly specific among muscle diseases, anti-cN1A antibodies are not 100% specific for IBM 3
- The specificity of anti-cN1A for IBM drops from 96% to 70% in patients who also have Sjögren's syndrome 4
IBM Pathophysiology and Other Antibodies
- IBM is characterized by CD8+ cytotoxic T cells and macrophages in the endomysium that surround and invade nonnecrotic muscle fibers expressing MHC class I 5
- Muscle degeneration in IBM shows rimmed vacuoles, nuclear and cytoplasmic inclusions, congophilic amyloid deposits, and phosphorylated tau proteins 5
- Unlike other inflammatory myopathies, IBM is increasingly considered a degenerative myopathy with inflammatory features 5
- Proinflammatory cytokines including type 1 interferons (α/β) and TNF-α circulate in IBM 5
Clinical Implications
- IBM is not associated with increased cancer risk, unlike other inflammatory myopathies 5
- Cancer screening is not routinely required in patients with verified IBM 5
- IBM is more common in patients with Sjögren's syndrome than in those without it (24% vs. 6%) 4
- IBM can co-occur with other conditions such as HIV or hepatitis C, which are associated with premature immune cell exhaustion 6
Diagnostic Considerations
- Careful clinical, electrophysiologic, and histopathologic correlation is required when evaluating patients with neuromuscular weakness and positive anti-cN1A antibodies 3
- Anti-cN1A antibodies have been reported in other conditions including motor neuron disease, making clinical correlation essential 3
- IBM typically does not respond to treatment, regardless of whether patients have associated Sjögren's syndrome 4