Institute for Experimental Endocrinology, Max Rubner Center for Cardiovascular Metabolic Renal Research, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, Zurich, Switzerland.
Front Immunol. 2024 Aug 8;15:1422781. doi: 10.3389/fimmu.2024.1422781. eCollection 2024.
The liver-derived selenium (Se) transporter selenoprotein P (SELENOP) declines in critical illness as a negative acute phase reactant and has recently been identified as an autoantigen. Hepatic selenoprotein biosynthesis and cotranslational selenocysteine insertion are sensitive to inflammation, therapeutic drugs, Se deficiency, and other modifiers. As severe burn injury induces a heavy inflammatory burden with concomitant Se depletion, we hypothesized an impairment of selenoprotein biosynthesis in the acute post-burn phase, potentially triggering the development of autoantibodies to SELENOP (SELENOP-aAb). To test this hypothesis, longitudinal serum samples from severely burned patients were analyzed over a period of six months. Newly occurring SELENOP-aAb were detected in 8.4% (7/83) of the burn patients, with onset not earlier than two weeks after injury. Prevalence of SELENOP-aAb was associated with injury severity, as aAb-positive patients have suffered more severe burns than their aAb-negative counterparts (median [IQR] ABSI: 11 [7-12] vs. 7 [5.8-8], = 0.023). Autoimmunity to SELENOP was not associated with differences in total serum Se or SELENOP concentrations. A positive correlation of kidney-derived glutathione peroxidase (GPx3) with serum SELENOP was not present in the patients with SELENOP-aAb, who showed delayed normalization of GPx3 activity post-burn. Overall, the data suggest that SELENOP-aAb emerge after severe injury in a subset of patients and have antagonistic effects on Se transport. The nature of burn injury as a sudden event allowed a time-resolved analysis of a direct trigger for new-onset SELENOP-aAb, which may be relevant for severely affected patients requiring intensified acute and long-term care.
肝脏来源的硒（Se）转运蛋白硒蛋白 P（SELENOP）在危重病中作为负急性相反应物下降，最近被确定为自身抗原。肝硒蛋白生物合成和共翻译硒代半胱氨酸插入对炎症、治疗药物、硒缺乏和其他修饰剂敏感。由于严重烧伤会引起沉重的炎症负担，同时伴有硒耗竭，我们假设在急性烧伤后阶段，硒蛋白生物合成受损，可能会引发针对 SELENOP（SELENOP-aAb）的自身抗体的产生。为了验证这一假设，我们对严重烧伤患者的纵向血清样本进行了长达六个月的分析。在 8.4%（7/83）的烧伤患者中检测到新出现的 SELENOP-aAb，发病时间不早于损伤后两周。SELENOP-aAb 的发生率与损伤严重程度相关，aAb 阳性患者的烧伤比 aAb 阴性患者更严重（中位数 [IQR] ABSI：11 [7-12] vs. 7 [5.8-8]， = 0.023）。SELENOP 自身免疫与总血清 Se 或 SELENOP 浓度无差异相关。在 SELENOP-aAb 患者中，肾源性谷胱甘肽过氧化物酶（GPx3）与血清 SELENOP 之间没有正相关，这些患者在烧伤后 GPx3 活性的恢复延迟。总的来说，这些数据表明，SELENOP-aAb 在烧伤患者的亚组中在严重损伤后出现，并对 Se 转运具有拮抗作用。烧伤损伤的突发性允许对新发病例 SELENOP-aAb 的直接触发因素进行时间分辨分析，这对于需要强化急性和长期护理的严重受影响患者可能具有重要意义。
