Pathomechanisms of anti –cytosolic 5′‐nucleotidase 1A autoantibodies in sporadic inclusion body myositis

This study investigated the pathogenic properties of anti‐cN1A autoantibodies in sIBM pathogenesis.
MethodsWe developed a cell‐based assay to detect anti‐cN1A autoantibodies, which we found in serum from patients with neuromuscular diseases including sIBM. We also investigated the clinicopathological differences between sIBM patients with and without the autoantibodies. We used passive in vitro and in vivo immunization models to evaluate the pathogenic role of the autoantibodies.
ResultsOf 67 patients with sIBM, 24 (35.8%) possessed anti‐cN1A autoantibodies as determined via our cell‐based assay. In the anti‐cN1A–positive group, the percentage of patients with hepatitis C virus antibodies was significantly lower and the mean area of type 2 myofibers was significantly smaller compared with the autoantibody‐negative group. In the in vitro passive immunization model, p62/SQSTM1 significantly increased in anti‐cN1A–positive sIBM immunoglobulin G (IgG)‐supplemented cells. In the in vivo passive immunization model, anti‐cN1A–positive sIBM IgG‐injected mice demonstrated p62/SQSTM1‐positive sarcoplasmic aggregates in myofibers, associated with macrophage infiltration.
InterpretationOur cell‐based assay is useful for anti‐cN1A autoantibodies detection. Patients with anti‐cN1A autoantibodies demonstrated unique clinicopathological features. In vitro and in vivo passive immunization model results suggest that anti‐cN1A autoantibodies may affect prot...

Source: Annals of Neurology - April 3, 2017 Category: Neurology Authors: Nozomu Tawara, Satoshi Yamashita, Xiao Zhang, Mai Korogi, Ziwei Zhang, Tsukasa Doki, Yoshimasa Matsuo, Shunya Nakane, Yasushi Maeda, Kazuma Sugie, Naoki Suzuki, Masashi Aoki, Yukio Ando Tags: Research Article Source Type: research