IL-1 Signaling Blockade in Human Lymphocytic Myocarditis

Lymphocytic myocarditis is characterized by infiltration of lymphocytes and macrophages. Current treatment for lymphocytic myocarditis is limited to corticosteroids and a proportion of patients progress to require heart transplantation or durable mechanical circulatory support within a year. Increasing attention is directed toward targeting pro-inflammatory mediators in myocarditis. One promising candidate is IL-1. Here, we investigated a patient with underlying autoimmune disease and biopsy confirmed lymphocytic myocarditis who was initially treated with corticosteroids and experienced clinical deterioration requiring temporary mechanical circulatory support. Rilonacept was consequently administered as a salvage therapy. Pathologically, rilonacept reduced inflammation and fibrosis. We performed spatial transcriptomics (ST) on formalin-fixed paraffin-embedded endomyocardial biopsy samples to further investigate how the cardiac immune landscape is modulated by rilonacept. Overall design: We performed spatial transcriptomics (ST) on formalin-fixed paraffin-embedded endomyocardial biopsy samples to further investigate how the cardiac immune landscape is modulated by rilonacept.

淋巴细胞性心肌炎（Lymphocytic myocarditis）以淋巴细胞及巨噬细胞浸润为核心病理特征。当前针对该病的治疗手段仅局限于糖皮质激素，且有部分患者可在1年内进展至需接受心脏移植或长期机械循环支持的阶段。学界愈发关注靶向心肌炎中的促炎介质，其中白细胞介素-1（IL-1）是颇具前景的候选治疗靶点。
我们报道1例合并基础自身免疫性疾病、经活检证实为淋巴细胞性心肌炎的患者：该患者初始接受糖皮质激素治疗后病情恶化，需临时机械循环支持，随后予以利纳西普（Rilonacept）作为挽救治疗方案。病理检测结果显示，利纳西普可减轻心肌炎症反应与纤维化程度。我们对福尔马林固定石蜡包埋的心内膜心肌活检样本实施空间转录组学（spatial transcriptomics, ST）分析，以进一步探究利纳西普对心脏免疫微环境的调控机制。
整体实验设计：我们对福尔马林固定石蜡包埋的心内膜心肌活检样本开展空间转录组学分析，以进一步解析利纳西普对心脏免疫微环境的调控作用。