中华儿科杂志
中華兒科雜誌
중화인과잡지
Chinese Journal of Pediatrics
2011年
9期
685-689
,共5页
徐晓军%汤永民%赵宁%宋华%杨世隆%石淑文%徐卫群%潘斌华%张玲燕%茅君卿%沈和萍%顾敏儿%夏静
徐曉軍%湯永民%趙寧%宋華%楊世隆%石淑文%徐衛群%潘斌華%張玲燕%茅君卿%瀋和萍%顧敏兒%夏靜
서효군%탕영민%조저%송화%양세륭%석숙문%서위군%반빈화%장령연%모군경%침화평%고민인%하정
淋巴组织细胞增多症,噬血细胞性%儿童%细胞因子类%诊断%预后%感染
淋巴組織細胞增多癥,噬血細胞性%兒童%細胞因子類%診斷%預後%感染
림파조직세포증다증,서혈세포성%인동%세포인자류%진단%예후%감염
Lymphohistiocytosis, hemophagocytic%Child%Cytokines%Diagnosis%Prognosis%Infection
目的 探讨Th1/Th2细胞因子检测在儿童噬血细胞综合征(HLH)诊断中的意义。方法 用流式细胞微球阵列术(CBA)检测50例HLH患儿血清的Th1/Th2细胞因子水平，包括γ干扰素(IFN-y)、肿瘤坏死因子(TNF)、白介素(IL)-10、IL-6、IL-4、IL-2共6种。同时设健康对照（250例健康儿童）及感染对照组（235例脓毒症患儿）。结果 50例患儿在HLH急性期各细胞因子水平的中位值如下：IFN-γ为1138.5(49.2～5000.0)ng/L、TNF为3.4(1.0 ～25.1 )ng/L、IL-10为740.5(26.5 ～ 5000.0) ng/L、IL-6为66.1 (3.9 ～ 4472.6) ng/L、IL-4为3.9( 1.0 ～ 32.8) ng/L、IL-2为4.0(1.0～51.1)ng/L，缓解后各细胞因子的水平明显下降。其中IFN-γ、IL-10和IL-6的急性期水平均明显高于缓解期和健康对照组（P均＜0.001）。而脓毒症组IFN-y、IL-10和IL-6水平分别为3.1(1.0～150.1)ng/L、46.5（3.1～5000.0）ng/L和251.3(8.4 ～ 5000.0) ng/L，其中IL-6水平明显高于HLH组(P＜0.001)，但IFN-γ和IL-10却显著低于HLH患儿（P均＜0.001）。根据ROC曲线设定HLH的细胞因子诊断标准如下：IFN-y＞ 100 ng/L,IL-10＞ 60 ng/L,且IFN-γ水平高于IL-6水平。在本研究队列的HLH和脓毒症患儿中，该标准对于HLH诊断的敏感度88.0％、特异度98.7％,阳性预测值93.6％、阴性预测值97.5％。结论IFN-y和IL-10显著升高,IL-6中等升高的Th1/Th2细胞因子谱对于HLH有很高的敏感度和特异度，对于HLH的诊断具有重要的参考价值。
目的 探討Th1/Th2細胞因子檢測在兒童噬血細胞綜閤徵(HLH)診斷中的意義。方法 用流式細胞微毬陣列術(CBA)檢測50例HLH患兒血清的Th1/Th2細胞因子水平，包括γ榦擾素(IFN-y)、腫瘤壞死因子(TNF)、白介素(IL)-10、IL-6、IL-4、IL-2共6種。同時設健康對照（250例健康兒童）及感染對照組（235例膿毒癥患兒）。結果 50例患兒在HLH急性期各細胞因子水平的中位值如下：IFN-γ為1138.5(49.2～5000.0)ng/L、TNF為3.4(1.0 ～25.1 )ng/L、IL-10為740.5(26.5 ～ 5000.0) ng/L、IL-6為66.1 (3.9 ～ 4472.6) ng/L、IL-4為3.9( 1.0 ～ 32.8) ng/L、IL-2為4.0(1.0～51.1)ng/L，緩解後各細胞因子的水平明顯下降。其中IFN-γ、IL-10和IL-6的急性期水平均明顯高于緩解期和健康對照組（P均＜0.001）。而膿毒癥組IFN-y、IL-10和IL-6水平分彆為3.1(1.0～150.1)ng/L、46.5（3.1～5000.0）ng/L和251.3(8.4 ～ 5000.0) ng/L，其中IL-6水平明顯高于HLH組(P＜0.001)，但IFN-γ和IL-10卻顯著低于HLH患兒（P均＜0.001）。根據ROC麯線設定HLH的細胞因子診斷標準如下：IFN-y＞ 100 ng/L,IL-10＞ 60 ng/L,且IFN-γ水平高于IL-6水平。在本研究隊列的HLH和膿毒癥患兒中，該標準對于HLH診斷的敏感度88.0％、特異度98.7％,暘性預測值93.6％、陰性預測值97.5％。結論IFN-y和IL-10顯著升高,IL-6中等升高的Th1/Th2細胞因子譜對于HLH有很高的敏感度和特異度，對于HLH的診斷具有重要的參攷價值。
목적 탐토Th1/Th2세포인자검측재인동서혈세포종합정(HLH)진단중적의의。방법 용류식세포미구진렬술(CBA)검측50례HLH환인혈청적Th1/Th2세포인자수평，포괄γ간우소(IFN-y)、종류배사인자(TNF)、백개소(IL)-10、IL-6、IL-4、IL-2공6충。동시설건강대조（250례건강인동）급감염대조조（235례농독증환인）。결과 50례환인재HLH급성기각세포인자수평적중위치여하：IFN-γ위1138.5(49.2～5000.0)ng/L、TNF위3.4(1.0 ～25.1 )ng/L、IL-10위740.5(26.5 ～ 5000.0) ng/L、IL-6위66.1 (3.9 ～ 4472.6) ng/L、IL-4위3.9( 1.0 ～ 32.8) ng/L、IL-2위4.0(1.0～51.1)ng/L，완해후각세포인자적수평명현하강。기중IFN-γ、IL-10화IL-6적급성기수평균명현고우완해기화건강대조조（P균＜0.001）。이농독증조IFN-y、IL-10화IL-6수평분별위3.1(1.0～150.1)ng/L、46.5（3.1～5000.0）ng/L화251.3(8.4 ～ 5000.0) ng/L，기중IL-6수평명현고우HLH조(P＜0.001)，단IFN-γ화IL-10각현저저우HLH환인（P균＜0.001）。근거ROC곡선설정HLH적세포인자진단표준여하：IFN-y＞ 100 ng/L,IL-10＞ 60 ng/L,차IFN-γ수평고우IL-6수평。재본연구대렬적HLH화농독증환인중，해표준대우HLH진단적민감도88.0％、특이도98.7％,양성예측치93.6％、음성예측치97.5％。결론IFN-y화IL-10현저승고,IL-6중등승고적Th1/Th2세포인자보대우HLH유흔고적민감도화특이도，대우HLH적진단구유중요적삼고개치。
Objective To illustrate the diagnostic value of Th1/Th2 cytokine pattern in childhood hemophagocytic lymphohistiocytosis ( HLH ) and its diagnostic accuracy. MethodThe BDTM CBA Human Th1/Th2 Cytokine Kit Ⅱ was used to measure the serum Th1 and Th2 cytokines, including Interferongamma ( IFN-γ), tumor necrosis factor ( TNF), interleukin ( IL)-10, IL-6, IL-4 and IL-2 in 50 patients with de novo HLH admitted to our hospital from Oct. 2005 to Aug. 2009. The above cytokine levels were also determined in 250 healthy volunteers and 235 patients with sepsis as controls. Result The primary features of these patients were prolonged high-grade fever (50/50) , hepatomegaly (44/50), splenomegaly ( 38/50 ), hemocytopenia (47/50), hyperferritinemia ( 49/50), coagulopathy ( 44/50 ), hemophagocytosis in bone marrow (42/50), liver dysfunction (42/50) and hypertriglyceridemia (42/50). The IFN-γ, TNF, IL-10, IL-6, IL-4 and IL-2 levels for healthy children were (4.6 ± 1.8) ng/L, (4.0 + 1.2) ng/L,(6.5 + 1.3) ng/L, (6.0 ± 1.5) ng/L, (2.9 + 0.8) ng/L and (2.6 + 0.7) ng/L, while the median levels of them in acute phase of HLH children were 1138.5 (49. 2-5000. 0) ng/L, 3.4 ( 1.0-25. 1 ) ng/L,740.5 (26.5-5000.0) ng/L, 66.1 (3.9-4472.6) ng/L, 3.9 (1.0-32.8) ng/L and 4.0 (1.0-51.1)ng/L, respectively. The cytokine levels decreased to 9. 1 ( 1.9-180. 1 ) ng/L, 2. 9 ( 1.0-1 1. 0) ng/L, 1 1. 4 (2.9-184.2) ng/L, 6.5 (1.0-44.8) ng/L, 2.7 (1.0-6.5) ng/Land4. 1 (1.0-12.0)ng/L respectively after remission. The IFN-γ, IL-10 and IL-6 levels in acute phase were significantly higher than those after remission and those of the healthy control ( P all ＜ 0. 001 ). IL-4, IL-2 and TNF slightly elevated or at normal range in acute phase of HLH. The patients with sepsis showed a different cytokine pattern, with an extremely high level of IL-6 ( median: 251.3 ng/L, range: 8.4- ＞5000. 0 ng/L) and moderately elevated level of IL-10 (median: 46. 5 ng/L, range: 3. 1-5000. 0 ng/L), whereas IFN-γ was only slightly elevated (median: 9. 2 ng/L, range: 1.3-498. 8 ng/L). When the criteria for HLH set as the following: IFN-γ＞ 100 ng/L, IL-10 ＞60 ng/L and the concentration of IFN-γhigher than that of IL-6, the specificity reached as high as 98. 7％ and the sensitivity was 88. 0％ for the diagnosis of HLH among patients with HLH and sepsis. Meanwhile, the positive predictive value (PPV) and negative predictive value (NPV) could reach 93.6％ and 97. 5％, respectively. Conclusion The significant increase of IFN-γand IL-10 with slightly increased level of IL-6 is a sensitive and specific cytokine pattern for childhood HLH, which is helpful for its diagnosis and differential diagnosis.
