Abstract：
BACKGROUND: Autoimmune lymphoproliferative syndrome (ALPS) is a rare primary immune disorder caused by defect of the extrinsic apoptotic pathway. The current diagnostic criteria combine clinical features and typical biomarkers but have not been the object of clear international consensus.
METHODS: We conducted a retrospective study on pediatric patients who were investigated for autoimmune cytopenia and/or lymphoproliferation at the CHU Sainte-Justine Hospital over 10 years. Patients were screened using the combination of TCRαβ+ CD4- CD8- \"double negative\" (DN) T cells and soluble plasmatic FAS ligand (sFASL).
RESULTS: Among the 398 tested patients, the median sFASL and DN T cells were 200 ng/mL and 1.8% of TCRαβ+ T cells, respectively. sFASL was highly correlated with vitamin B12 levels. We identified five patients diagnosed with ALPS for whose sFASL and vitamin B12 levels were the more discriminating biomarkers. While ALPS diagnostic criteria had high sensibility, their predictive value remained low.
CONCLUSIONS: sFASL level can efficiently discriminate patients with ALPS when using the appropriate thresholds. Our study highlights the need for an international consensus to redefine the place and threshold of biological biomarkers for ALPS diagnosis.
METHODS: We conducted a retrospective study on pediatric patients who were investigated for autoimmune cytopenia and/or lymphoproliferation at the CHU Sainte-Justine Hospital over 10 years. Patients were screened using the combination of TCRαβ+ CD4- CD8- \"double negative\" (DN) T cells and soluble plasmatic FAS ligand (sFASL).
RESULTS: Among the 398 tested patients, the median sFASL and DN T cells were 200 ng/mL and 1.8% of TCRαβ+ T cells, respectively. sFASL was highly correlated with vitamin B12 levels. We identified five patients diagnosed with ALPS for whose sFASL and vitamin B12 levels were the more discriminating biomarkers. While ALPS diagnostic criteria had high sensibility, their predictive value remained low.
CONCLUSIONS: sFASL level can efficiently discriminate patients with ALPS when using the appropriate thresholds. Our study highlights the need for an international consensus to redefine the place and threshold of biological biomarkers for ALPS diagnosis.
摘要：
背景：自身免疫淋巴组织增生综合征（ALPS）是一种罕见的由外源性凋亡途径缺陷引起的原发性免疫疾病。当前的诊断标准结合了临床特征和典型的生物标志物，但尚未成为国际上明确共识的对象。
方法：我们对在CHUSainte-Justine医院进行了为期10年的自身免疫性血细胞减少和/或淋巴增生的儿科患者进行了回顾性研究。使用TCRαβCD4-CD8-“双阴性”（DN）T细胞和可溶性血浆FAS配体（sFASL）的组合筛选患者。
结果：在398名受检患者中，sFASL和DNT细胞的中位数为200ng/mL，占TCRαβ+T细胞的1.8%，分别。sFASL与维生素B12水平高度相关。我们确定了5例诊断为ALPS的患者，其sFASL和维生素B12水平是更有区别的生物标志物。ALPS诊断标准敏感性高,他们的预测价值仍然很低。
结论：sFASL水平在使用适当的阈值时可以有效区分ALPS患者。我们的研究强调了国际共识的必要性，以重新定义ALPS诊断的生物标志物的位置和阈值。
方法：我们对在CHUSainte-Justine医院进行了为期10年的自身免疫性血细胞减少和/或淋巴增生的儿科患者进行了回顾性研究。使用TCRαβCD4-CD8-“双阴性”（DN）T细胞和可溶性血浆FAS配体（sFASL）的组合筛选患者。
结果：在398名受检患者中，sFASL和DNT细胞的中位数为200ng/mL，占TCRαβ+T细胞的1.8%，分别。sFASL与维生素B12水平高度相关。我们确定了5例诊断为ALPS的患者，其sFASL和维生素B12水平是更有区别的生物标志物。ALPS诊断标准敏感性高,他们的预测价值仍然很低。
结论：sFASL水平在使用适当的阈值时可以有效区分ALPS患者。我们的研究强调了国际共识的必要性，以重新定义ALPS诊断的生物标志物的位置和阈值。
