033 Bullous pemphigoid autoantibodies induce keratinocyte PAI-1 expression resulting in decreased plasmin activation
نویسندگان
چکیده
Bullous pemphigoid (BP) has been associated with an increase in venous thromboembolism due to impaired fibrinolysis. As plasma levels of plasminogen activator inhibitor type 1 (PAI-1) are elevated BP patients, this represents one possible mechanism. We sought better understand the role autoantibodies inducing a prothrombotic state. first reviewed our previous RNA-seq database BP-IgG treated keratinocytes relative controls, confirming overexpression SERPINE1 (Log2fold (1.01 P-adjusted < 0.0001). To confirm these results at protein level, we next primary human overnight IgG from patients and normal controls performed Luminex assay on supernatants revealing 28-fold supernatant PAI-1 control-IgG (P whether keratinocyte would carry net anti-fibrinolytic effect, plasmin activation assay. In assay, cleavage fluorogenic substrate. Recombinant was or keratinocytes, fluorometric activity measured 30 minutes. Relative fluorescence units (RFU) were significantly increased versus = 0.02), indicating inhibition keratinocytes. These findings reveal direct mechanism by which induce state through expression Further research is needed determine additional mechanisms blister formation contribute towards
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ژورنال
عنوان ژورنال: Journal of Investigative Dermatology
سال: 2022
ISSN: ['1523-1747', '0022-202X']
DOI: https://doi.org/10.1016/j.jid.2022.05.087