Inclusion‐body myositis and primary Sjögren syndrome: mechanisms for shared etiologies

Abstract

Herein we report a case of sporadic inclusion-body myositis (sIBM) occurring at an unusually young age in a patient with primary Sjögren syndrome, and use the case to explore possible shared mechanisms for disease susceptibility. Possible factors may include the association of both conditions with the 8.1 ancestral haplotype; the presence of anti-cN1A antibodies, which, although considered specific for sIBM, are also seen in pSS; and the shared association with T-cell large granular lymphocyte leukemia (T-LGLL). Further evaluation of this patient did in fact reveal underlying T-LGLL and mechanisms by which T cells in sIBM may escape immune regulation and contribute to disease phenotype are explored. Despite myofiber infiltration with CD8-positive T cells in sIBM, and, although sIBM is traditionally considered treatment-refractory, we report a significant response to the anti-CD20 monoclonal antibody, rituximab, and discuss possible mechanisms by which this response may be mediated. K E Y W O R D Santi-cN1A, inclusion-body myositis, primary Sjögren syndrome, rimmed vacuoles, rituximab

Inclusion body myositis in an older patient

“…3,8 A limitation is that this named autoantibody is thought to be a 'myositisassociated' antibody, rather than it necessarily being a 'myositis-specific' antibody. 3,8,12 This is because it has also been observed in other conditions such as Sjögren syndrome and systemic lupus erythematosus (SLE). 3,8,12 The use of magnetic resonance imaging (MRI) in sIBM can also be used to support the diagnostic formulation i.e.…”

“…1,3,8,9 It is usually seen in the over 50-year adult population, and tends to affect males more than females. 3,8,7,[10][11][12] The prevalence of IBM is varies from region to region e.g. due to factors like a tendency for the diagnosis to be missed or delayed, lack of awareness of this condition among generalist healthcare professionals, evolving diagnostic criteria, as well as incremental advances in molecular medicine and histopathology.…”

“…8 In IBM, there is a gradual progression of (often initially) painless muscle weakness, which is of asymmetric nature, and leading to significant functional impairment/reduction. 8,12,13 Affected adults typically present with weakness of the following muscle groups: knee extensors (e.g. with individuals having difficulty standing or walking, thereby leading to falls); long finger flexors usually on the non-dominant side (e.g.…”

“…resulting in dysphagia, albeit less often as a primary but in the later stages potentially resulting in weight loss and aspiration pneumonia). 8,9,12 The diagnostic criteria for IBM require: the presence of an asymmetric pattern of clinical weakness e.g. either knee extensors or finger flexor; muscle biopsy confirming the presence of rimmed vacuoles (although this may be absent in up to 20% of individuals), or noting the invasion by Tcells of non-necrotic muscle fibres and the presence of endomysial inflammation.…”

“…either knee extensors or finger flexor; muscle biopsy confirming the presence of rimmed vacuoles (although this may be absent in up to 20% of individuals), or noting the invasion by Tcells of non-necrotic muscle fibres and the presence of endomysial inflammation. 3,8,12 The presence of anti-cytosolic 5'-nucleotidase 1A (cN1A) autoantibody (described/discovered in year 2013) can also be a helpful aid in establishing the diagnosis of sIBM i.e. when used alongside the criteria above.…”