All Publications

  • Characterization of Monoclonal Anti-PAD4 Autoantibodies from Rheumatoid Arthritis Patients: Functional Implications for Citrullination and Disease Progression Gomez, A., Kongpachith, S., Lingampalli, N., Cisar, C., Robinson, W. H. WILEY. 2018
  • Silencing of Dok-7 in Adult Rat Muscle Increases Susceptibility to Passive Transfer Myasthenia Gravis AMERICAN JOURNAL OF PATHOLOGY Gomez, A. M., Stevens, J. A., Mane-Damas, M., Molenaar, P., Duimel, H., Verheyen, F., Cossins, J., Beeson, D., De Baets, M. H., Losen, M., Martinez-Martinez, P. 2016; 186 (10): 2559-2568


    Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies that target proteins at the neuromuscular junction, primarily the acetylcholine receptor (AChR) and the muscle-specific kinase. Because downstream of kinase 7 (Dok-7) is essential for the full activation of muscle-specific kinase and consequently for dense clustering of AChRs, we hypothesized that reduced levels of Dok-7 increase the susceptibility to passive transfer MG. To test this hypothesis, Dok-7 expression was reduced by transfecting shRNA-coding plasmids into the tibialis anterior muscle of adult rats by in vivo electroporation. Subclinical MG was subsequently induced with a low dose of anti-AChR monoclonal antibody 35. Neuromuscular transmission was significantly impaired in Dok-7-siRNA-electroporated legs compared with the contralateral control legs, which correlated with a reduction of AChR protein levels at the neuromuscular junction (approximately 25%) in Dok-7-siRNA-electroporated muscles, compared with contralateral control muscles. These results suggest that a reduced expression of Dok-7 may play a role in the susceptibility to passive transfer MG, by rendering AChR clusters less resistant to the autoantibody attack.

    View details for DOI 10.1016/j.ajpath.2016.05.025

    View details for Web of Science ID 000384389400007

    View details for PubMedID 27658713