Seropositivity for NT5c1A antibody in sporadic inclusion body myositis predicts more severe motor, bulbar and respiratory involvement

Abstract

Objectives To explore phenotypic differences between individuals with sporadic inclusion body myositis (sIBM) who are seropositive for the NT5c1A antibody compared with those who are seronegative. Methods Cross-sectional clinical, serological and functional analysis in 25 consecutive participants with sIBM. Results All participants met criteria for clinically defined or probable sIBM. 18 of 25 participants with sIBM (72%) were seropositive for the NT5c1A antibody. No differences between median age and duration of illness between the two groups were seen. Females have higher odds of being seropositive (OR=2.30). Participants with seropositive sIBM took significantly longer to get up and stand (p=0.012). There were no significant differences between the two groups in terms of distance covered on a 6 min walk. Seropositive participants were more likely to require assistive devices such as a walker or wheelchair for mobility (OR=23.00; p=0.007). A number of secondary (exploratory) outcomes were assessed. NT5c1A seropositive sIBM cases had lower total Medical Research Council (MRC) sum score and MRC sum score on the right (p=0.03 and 0.02, respectively). Participants with the NT5c1A antibody were significantly more likely to have symptoms of dysphagia (OR=10.67; p=0.03) and reduced forced vital capacity (p=0.005). Facial weakness occurred in 50% of seropositive participants while it was only seen in 14% of seronegative participants. Conclusions Even though the small sample size limits definite conclusions, our cross-sectional study showed seropositivity to the NT5c1A antibody is associated with greater motor and functional disability in sIBM. The study also suggests more prominent bulbar, facial and respiratory involvement in individuals positive for NT5c1A antibodies.

Development and evaluation of a standardized ELISA for the determination of autoantibodies against cN-1A (Mup44, NT5C1A) in sporadic inclusion body myositis

“…So far, only one study has provided data indicating that anti-cN-1A seropositivity may be associated with a more aggressive form of IBM, including more prominent motor, bulbar and respiratory involvement [37]. …”

Integrated classification of inflammatory myopathies

“…In fact, the presence of the anti-NT5C1A autoantibody is associated with fewer rimmed vacuoles, highlighting the correlation with specific myopathological features [45][46][47][48][49][50]. In addition, the presence of the antibody also predicts more severe motor, bulbar and respiratory involvement [51]. Additional autoantibodies have been recently discovered, and their frequency and relevance remain to be defined [52][53][54][55].…”

Anti‐NT5C1A autoantibodies for the diagnosis and study of the pathogenesis of sporadic inclusion body myositis

“…The presence of anti‐cN1A autoantibodies also suggests an immunological pathomechanism for sIBM. With regard to the clinicopathological features of sIBM patients with anti‐cN1A autoantibodies, an initial study suggested that seropositivity for the anti‐cN1A autoantibodies was associated with greater motor and functional disability: sIBM patients with the autoantibodies showed more prominent bulbar, facial and respiratory symptoms . In our investigation, the percentage of patients with hepatitis C virus antibodies was significantly lower, and the mean area of type 2 myofibers was significantly smaller in the anti‐cN1A‐positive group compared with the autoantibody‐negative group .…”

“…Furthermore, Greenberg reported that combination assays for all autoantibody isotypes (immunoglobulin [Ig]G, IgM and IgA) improved the diagnostic sensitivity for sIBM up to 76% . Since the identification of the presence of anti‐cN1A autoantibodies in sIBM, different methodologies for their detection have emerged, such as immunoprecipitation, immunoblotting with human skeletal muscle extracts or lysates of cN1A‐expressing human embryonic kidney 293 cells, and enzyme‐linked immunosorbent assays with recombinant full‐length cN1A protein or synthetic peptides derived from cN1A . In Table , we summarized the frequencies of seropositivity for anti‐cN1A autoantibodies in various diseases using different methodologies.…”