Patients with systemic autoimmune diseases make specific autoantibodies that are directed against self structures. According to one view, these autoantibodies arise as a result of an immune response to foreign antigens such as infectious agents that share, by molecular mimicry, common structures with host proteins. An alternative view is that the target autoantigen itself initiates, selects, and sustains autoantibody synthesis. We show here that anti-Jo-1 autoantibodies directed against histidyl-tRNA synthetase in the human autoimmune muscle disease polymyositis undergo, in addition to spectrotype broadening and class switching, the sine qua non of an immune response to the target antigen-affinity maturation to that antigen. We demonstrate further that these autoantibodies, unlike anti-synthetase antibodies induced in mice immunized with heterologous antigen, bind only nonlinear epitopes on the native human synthetase that remain exposed when the enzyme is complexed to tRNAHi. These data suggest that the native target autoantigen itself has played a direct role in selecting and sustaining the autoantibody response and sharply restrict the time and the way in which a molecular mimic might act to provoke autoantibodies.

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Purpose:The Interprofessional Educational (IPE) Clinic at Duke is a clinical experience that has allowed an interprofessional team, including health professions students, to care for patients in the emergency department (ED) since 2015. COVID-19 presented fundamental challenges to the structure of this experience, such as student restrictions on attending clinical experiences and limitations on the number of providers in a patient room, which necessitated a transition from face-to-face encounters to virtual ones. Materials and Methods: As a result, two virtual experiences were implemented; one was based in the ED with in-person faculty and patients with virtual learners and one staffed by ambulatory providers engaging in telehealth clinics. These experiences sought to provide an interprofessional clinical experience for students while following appropriate safety guidelines. Surveys were distributed to students post-clinic to gather student demographics and their feedback regarding the experience. Additionally, faculty preceptors provided insight into the experience, especially regarding logistics and infrastructure. Results: The virtual experiences successfully allowed teams of students to participate remotely in aspects of care including history taking, physical assessments, and medical decision-making. Additionally, the virtual care team structure allowed for senior students to mentor junior learners and for faculty members to provide point of care feedback. Students gained practical experience in telehealth that included logistics and challenges of providing virtual care and appreciating how technological barriers such as lack of access to internetconnected devices can be a source of disparity. Conclusion:The COVID-19 pandemic required the reconfiguration of an in-person clinical experience to a virtual experience and this pivot was well received by students and faculty. The lessons learned can be generalizable to other professional schools who may be seeking to develop an interprofessional clinical experience and are exploring telehealth options.