Complement factor I: Regulatory nexus, driver of immunopathology, and therapeutic.

Complement factor I (FI) is the nexus for classical, lectin and alternative pathway complement regulation. FI is an 88 kDa plasma protein that circulates in an inactive configuration until it forms a trimolecular complex with its cofactor and substrate whereupon a structural reorganization allows the catalytic triad to cleave its substrates, C3b and C4b. In keeping with its role as the master complement regulatory enzyme, deficiency has been linked to immunopathology. In the setting of complete FI deficiency, a consumptive C3 deficiency results in recurrent infections with encapsulated microorganisms. Aseptic cerebral inflammation and vasculitic presentations are also less commonly observed. Heterozygous mutations in the factor I gene (CFI) have been demonstrated to be enriched in atypical haemolytic uraemic syndrome, albeit with a very low penetrance. Haploinsufficiency of CFI has also been associated with decreased retinal thickness and is a strong risk factor for the development of age-related macular degeneration. Supplementation of FI using plasma purified or recombinant protein has long been postulated, however, technical difficulties prevented progression into clinical trials. It is only using gene therapy that CFI supplementation has reached the clinic with GT005 in phase I/II clinical trials for geographic atrophy.

Risk of sudden cardiac death in a case of spontaneous coronary artery dissection presenting with thyroid storm.

OBJECTIVE: Spontaneous coronary artery dissection (SCAD) is a spontaneous separation of the coronary artery wall whose etiology appears to be poorly understood. SCAD is a rare cause of acute coronary syndromes, and it is a life-threatening condition. CASE REPORT: We report the case of a young woman who developed SCAD during a thyroid storm (TS). RESULTS: To the best of our knowledge, this is the first reported case of SCAD during a TS, and it suggests a possible association between high levels of circulating thyroid hormones and SCAD susceptibility. CONCLUSIONS: Early identification of SCAD predisposing factors is important to identify high-risk patients. In patients presenting to the emergency department because of chest pain with a history of dysthyroidism, early determination of thyroid hormones and troponin could prevent certain forms of sudden cardiac death.