Center for Autoinflammatory Diseases and Immunodeficiencies, IRCCS G. Gaslini.
Clinic of Pediatrics and Rheumatology, IRCCS G. Gaslini and University of Genoa.
Rheumatology (Oxford). 2022 Feb 2;61(2):696-704. doi: 10.1093/rheumatology/keab361.
To test the usefulness of an extended panel of lymphocyte subsets in combination with Oliveira's diagnostic criteria for the identification of autoimmune lymphoproliferative syndrome (ALPS) in children referred to a paediatric rheumatology centre.
Patients referred from 2015 to 2018 to our rheumatology unit for an autoimmune or autoinflammatory condition were retrospectively analysed. Oliveira's required criteria [chronic lymphoproliferation and elevated double-negative T (DNT)] were applied as first screening. Flow cytometry study included double-negative CD4-CD8-TCRαβ+ T lymphocytes (DNT), CD25+CD3+, HLA-DR+CD3+ T cells, B220+ T cells and CD27+ B cells. Data were analysed with a univariate logistic regression analysis, followed by a multivariate analysis. Sensitivity and specificity of the Oliveira's required criteria were calculated.
A total of 264 patients were included in the study and classified as: (i) autoimmune diseases (n = 26); (ii) juvenile idiopathic arthritis (JIA) (35); (iii) monogenic systemic autoinflammatory disease (27); (iv) periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome (100); (v) systemic undefined recurrent fever (45); (vi) undetermined-systemic autoinflammatory disease (14); or (vii) ALPS (17). Oliveira's required criteria displayed a sensitivity of 100% and specificity of 79%. When compared with other diseases the TCRαβ+B220+ lymphocytes were significantly increased in ALPS patients. The multivariate analysis revealed five clinical/laboratory parameters positively associated to ALPS: splenomegaly, female gender, arthralgia, elevated DNT and TCRαβ+B220+ lymphocytes.
Oliveira's required criteria are useful for the early suspicion of ALPS. TCRαβ+B220+ lymphocytes should be added in the diagnostic work-up of patients referred to the paediatric rheumatology unit for a suspected autoimmune or autoinflammatory condition, providing a relevant support in the early diagnosis of ALPS.
测试扩展的淋巴细胞亚群组合与 Oliveira 诊断标准在儿科风湿病中心就诊的自身免疫性淋巴增生综合征 (ALPS) 患者中的应用价值。
回顾性分析了 2015 年至 2018 年因自身免疫或炎症性疾病就诊于我院风湿科的患者。首先应用 Oliveira 的必需标准[慢性淋巴细胞增生和升高的双阴性 T（DNT）]进行初步筛选。流式细胞术研究包括双阴性 CD4-CD8-TCRαβ+T 淋巴细胞（DNT）、CD25+CD3+、HLA-DR+CD3+T 细胞、B220+T 细胞和 CD27+B 细胞。采用单变量逻辑回归分析和多变量分析对数据进行分析。计算 Oliveira 的必需标准的敏感性和特异性。
共纳入 264 例患者，分为：（i）自身免疫性疾病（n=26）；（ii）幼年特发性关节炎（JIA）（35）；（iii）单基因系统性自身炎症性疾病（27）；（iv）周期性发热、口疮性口炎、咽炎和淋巴结炎综合征（100）；（v）全身性未明原因复发性发热（45）；（vi）未明系统性自身炎症性疾病（14）或（vii）ALPS（17）。Oliveira 的必需标准显示出 100%的敏感性和 79%的特异性。与其他疾病相比，ALPS 患者的 TCRαβ+B220+淋巴细胞明显增加。多变量分析显示，与 ALPS 相关的五个临床/实验室参数为：脾肿大、女性、关节炎、升高的 DNT 和 TCRαβ+B220+淋巴细胞。
Oliveira 的必需标准有助于早期怀疑 ALPS。TCRαβ+B220+淋巴细胞应添加到对儿科风湿病中心就诊的疑似自身免疫或自身炎症性疾病患者的诊断评估中，为 ALPS 的早期诊断提供重要支持。
