Platelet activation in stevens-johnson syndrome and toxic epidermal necrolysis

Summary: Abstract Body: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening conditions often triggered by drugs. This study aimed to investigate innate immunity in SJS/TEN. We stimulated HaCat cells with serum from TEN patients or healthy controls (HC) and performed liquid proteomics analysis. A total of 42 altered proteins from 440 targeted were identified, and gene ontology analysis indicated that there were significant differences in platelet degranulation and alpha granules. Our cluster analysis identified platelet factor 4 (PF4/CXCL4) and neutrophil-activating peptide 2 (NAP-2/CXCL7) as notably altered proteins. Then, we enrolled 22 SJS/TEN patients and three times as many healthy controls, measuring serum levels of CXCL4 and CXCL7. CXCL4 levels were 25.93 times higher in SJS/TEN patients (8270±1116 ng/ml) compared to controls (318.9±80.68 ng/ml), while CXCL7 levels were 3.58 times higher (4776±330 ng/ml vs. 1334±272.4 ng/ml). Both CXCL4 and CXCL7 significantly decreased at the recovery stage (p<0.05). We found a positive correlation between CXCL4/CXCL7 levels at onset and IL-15 concentration (CXCL4: r=0.6758, p<0.05; CXCL7: r=0.5632, p<0.05), a predictor of SJS/TEN severity. Elevated CXCL4 correlated with TNF-α (r=0.4487, p<0.05) and Granzyme B (r=0.6484, p<0.05). In a cohort of 42 SJS/TEN patients, we analyzed platelet indices and found significant alterations at onset compared to recovery (p<0.05). Furthermore, we injected mice with recombinant CXCL4 (500 ng/mouse), CXCL7 (500 ng/mouse), or both. Inflammatory cell recruitment was assessed by multiplex immunohistochemistry (mIHC). Compared to PBS-treated mice, we observed significant increases in total leukocytes, CD4+ T cells, CD8+ T cells, and neutrophils in the skin of CXCL4-injected mice. Given that these chemokines serve as biomarkers of platelet activation, our findings suggest that platelet activation plays a crucial role in SJS/TEN pathophysiology, warranting further studies using humanized mouse models. Chunlan Zhang¹, Dandan Zang², Feng Wang¹ 1. Dermatology, Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China. 2. Center for Scientific Research, Anhui Medical University, Hefei, Anhui, China. Innate Immunity, Microbiology, and Microbiome