OBJECTIVE: Sporadic inclusion body myositis (sIBM), an intractable progressive muscle disease, frequently occurs in older persons. sIBM pathogenesis may involve protein degradation dysfunction and immune abnormalities. Autoantibodies recognizing cytosolic 5'-nucleotidase 1A (cN1A) were found in plasma and serum from sIBM patients. However, whether anti-cN1A autoantibodies play a pathogenic role in sIBM is controversial. This study investigated the pathogenic properties of anti-cN1A autoantibodies in sIBM pathogenesis. METHODS: We 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. RESULTS: Of 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. INTERPRETATION: Our 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 protein degradation in myofibers. Ann Neurol 2017;81:512-525.
OBJECTIVE: Sporadic inclusion body myositis (sIBM), an intractable progressive muscle disease, frequently occurs in older persons. sIBM pathogenesis may involve protein degradation dysfunction and immune abnormalities. Autoantibodies recognizing cytosolic 5'-nucleotidase 1A (cN1A) were found in plasma and serum from sIBM patients. However, whether anti-cN1A autoantibodies play a pathogenic role in sIBM is controversial. This study investigated the pathogenic properties of anti-cN1A autoantibodies in sIBM pathogenesis. METHODS: We 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. RESULTS: Of 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. INTERPRETATION: Our 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 protein degradation in myofibers. Ann Neurol 2017;81:512-525.
Authors: Richard M Yeker; Iago Pinal-Fernandez; Lisa G Rider; Andrew L Mammen; Takayuki Kishi; Katherine Pak; Ira N Targoff; Frederick W Miller Journal: Ann Rheum Dis Date: 2018-01-23 Impact factor: 19.103
Authors: Anke Rietveld; Luuk L van den Hoogen; Nicola Bizzaro; Sofie L M Blokland; Cornelia Dähnrich; Jacques-Eric Gottenberg; Gunnar Houen; Nora Johannsen; Thomas Mandl; Alain Meyer; Christoffer T Nielsen; Peter Olsson; Joel van Roon; Wolfgang Schlumberger; Baziel G M van Engelen; Christiaan G J Saris; Ger J M Pruijn Journal: Front Immunol Date: 2018-06-05 Impact factor: 7.561
Authors: Adam Amlani; May Y Choi; Mark Tarnopolsky; Lauren Brady; Ann E Clarke; Ignacio Garcia-De La Torre; Michael Mahler; Heinrike Schmeling; Claire E Barber; Michelle Jung; Marvin J Fritzler Journal: Front Immunol Date: 2019-04-09 Impact factor: 7.561
Authors: R Hal Scofield; Valerie M Lewis; Joshua Cavitt; Biji T Kurien; Shervin Assassi; Javier Martin; Olga Gorlova; Peter Gregersen; Annette Lee; Lisa G Rider; Terrance O'Hanlon; Simon Rothwell; James Lilleker; Yuta Kochi; Chikacshi Terao; Ann Igoe; Wendy Stevens; Joanne Sahhar; Janet Roddy; Maureen Rischmueller; Sue Lester; Susanna Proudman; Sixia Chen; Matthew A Brown; Maureen D Mayes; Janine A Lamb; Frederick W Miller Journal: ACR Open Rheumatol Date: 2022-03-29