Citations

ABSTRACT Autoantibody internalization has been implicated in autoimmune disease pathogenesis, yet its mechanisms, and generality across different diseases, cell types, and affected tissues remain poorly defined. Using bulk RNA sequencing, we identified reproducible, autoantibody-specific transcriptomic signatures consistent with autoantigen dysfunction in muscle biopsies from patients with anti-Mi2 dermatomyositis and anti-PM/Scl scleromyositis across independent cohorts. Electroporation of purified patient IgG into primary cultures of healthy cells was sufficient to induce the corresponding transcriptomic programs in vitro . Direct immunofluorescence demonstrated immunoglobulin internalization into subcellular compartments matching the localization of the autoantigen in different affected tissues. Spatial transcriptomic analyses revealed that antibody-secreting cells translocated cytoplasmic material (i.e., immunoglobulin RNA) into adjacent affected cells expressing autoantibody-specific transcripts. The disease-specific transcripts were present not only in muscle fibers, but also in other cells, including macrophages, endothelial cells, and fibroblasts. Autoantibody-induced transcriptomic programs were associated with cell damage and autoantibody-specific reactive inflammatory programs, including activation of type I interferon and TGF-ß1 signaling in anti-Mi2 dermatomyositis and activation of type II interferon in anti-PM/Scl scleromyositis. Antibody internalization was also observed in different tissues from patients with other autoimmune diseases, including anti-U1RNP mixed connective tissue disease, anti-Ku overlap syndrome, and anti-Scl70 systemic sclerosis. Together, these findings establish autoantibody internalization as a shared pathogenic mechanism across diverse autoimmune diseases, providing a unifying framework for conditions driven by autoantibodies against intracellular antigens.

Objective: Despite excellent functional outcomes after shoulder stabilization surgery, a substantial number of patients fail to return to sports (RTS) at the preinjury level. The psychological factors affecting RTS postsurgery have been underexplored. This scoping review aimed to identify and analyze potential psychological factors influencing the decision to RTS after shoulder stabilization surgery. Data Sources: We reviewed the EBSCOhost/SPORTDiscus, PubMed/Medline, Scopus, EMBASE, and Cochrane Library databases for studies on patients with anterior glenohumeral instability who underwent stabilization surgery. We included studies that reported on RTS and considered the psychological factors influencing the decision to return. Main Results: Our analysis comprised 21 articles involving 2073 patients. Psychological factors influencing RTS after surgery were categorized within the framework of transactional stress and coping model. Primary appraisal factors, such as fear of reinjury, kinesiophobia, and anxiety, emerged as significant influencers. In addition, we explored factors related to social support, self-determination, motivation, competing interests, and advanced age. Assessment tools were used to evaluate the psychological readiness for RTS. Conclusions: This scoping review identified fear of reinjury and kinesiophobia as important psychological barriers to returning to sports after shoulder stabilization surgery. The limited use of psychological assessment tools and lack of comparative studies have restricted robust conclusions. Level of Evidence: Level IV, Scoping review.