The cGAS-STING Pathway, Ion Channel Dysregulation, and Immune Responses: Implications for Autoimmunity, Inflammation, Long COVID, and Post-Vaccination Responses

Ion channel dysfunction plays a pivotal role in neurological and autoimmune disorders, often leading to misdiagnoses due to symptom overlap with conditions like acute inflammatory demyelinating polyneuropathy, dysautonomia, postural orthostatic tachycardia syndrome (POTS), and small fiber neuropathy. This paper presents a theoretical framework linking ion channelopathies to autoimmunity through cGAS-STING pathway activation and macrophage polarization. It further explores how post-viral immune responses, including those in Long COVID and vaccine-related responses, may in rare instances, contribute to ion channel dysfunction, exacerbating autonomic and neuromuscular symptoms. The intersection of these mechanisms complicates diagnostic accuracy and therapeutic strategies. Sex-based differences and ethnic genetic predispositions in immune regulation are examined, offering insight into population-specific variations in immune-mediated ion channelopathies. This work highlights the need for improved diagnostic criteria and specific therapeutic interventions to address immune-driven ion channel dysfunction.