肝病患者 IgA 和 sIgA 含量变化的临床意义

摘要

目的: 探讨肝脏病变时IgA和sIgA对临床诊断的意义.

方法: 肝病患者共168例, 包括急性肝炎35例, 慢性重症肝炎9例, 慢性肝炎67例, 肝硬化57例, 用免疫速率比浊法检测IgA, 用放射免疫分析法检测sIgA.

结果: 肝脏患者粪便IgA, sIgA均显著高于正常对照组 (IgA: 100±47, 251±178, 80±24, 145±164 mg/L vs <67 mg/L,P<0.01; sIgA: 88±96, 326±237, 88±121, 104±109 mg/L vs 13±10 mg/L, P<0.01), IgA和sIgA呈显著正相关 (r = 0.4371, P<0.01). 血清中IgA和sIgA显著高于正常对照组( IgA: 3.1±1.1, 3.4±1.8, 3.3±1.7, 4.9±3.3 g/L vs1.6±0.2 g/L, P<0.01; sIgA: 31.1±25.8, 80.3±25.4, 30.5±24.1, 50.0±20.5 g/L vs 23.4±8.2 g/L, P<0.01 或 P<0.05), 便IgA和sIgA与血清中IgA, sIgA含量无相关性, 血清中IgA与血清中sIgA亦无相关性. 慢性肝炎、慢性重症肝炎、肝硬化患者血清sIgA与碱性磷酸酶(r = 0.523 0, P<0.01)、总胆红素 (r = 0.458 1, P<0.01)有相关性; 急性肝炎血清sIgA与ALT(r = 0.469 2, P<0.01)、总胆红素(r = 0.426 5, P<0.01)有相关性.

结论: 检测粪便中和血清中IgA和sIgA对肝脏的临床诊断有重要的临床意义.

关键词: IgA; sIgA; 肝病

Changes of IgA and sIgA and its clinical significant in hepatic diseases

Dong-Yan Liu, Pei Liu

Dong-Yan Liu, Pei Liu, Department of Infectious Diseases, the Second Affiliated of China Medical University, Shenyang 110004, Liaoning Province, China

Correspondence to: Pei Liu, Department of Infectious Diseases, the Second Affiliated Hospital of China Medical University, 36 Sanhao Street, Shenyang 110004, Liaoning Province, China. syliupei2003@yahoo.com.cn

Received: June 30, 2005
Revised: July 7, 2005
Accepted: July 15, 2005
Published online: September 28, 2005

Abstract

AIM: To investigate the values of IgA and sIgA detection in the clinical diagnosis of hepatic diseases.

METHODS: Patients with acute hepatitis (AH, n = 35), chronic severe hepatitis (CSH, n = 9), chronic hepatitis (CH, n = 67) and liver cirrhosis (LC, n = 57) were involved. The level of IgA was assayed by rate nephelometry, and the level of sIgA was detected by radioimmunoassay.

RESULTS: The levels of fecal IgA and sIgA were notably elevated in patients with AH, CSH, CH and LC as compared with those in the controls (IgA: 100±47, 251±178, 80±24, 145±164 mg/L vs <67 mg/L, P < 0.01; sIgA: 88±96, 326±237, 88±121, 104±109 mg/L vs 13±10 mg/L, P < 0.01). IgA was positively correlated with sIgA(r = 0.4371, P < 0.01). The levels of serum IgA and sIgA were markedly increased in patients with AH, CSH, CH and LC as compared with those in the controls (IgA: 3.1±1.1, 3.4±1.8, 3.3±1.7, 4.9±3.3 g/L vs 1.6±0.2 g/L, P < 0.01; sIgA: 31.1±25.8, 80.3±25.4, 30.5±24.1, 50.0±20.5 µg/L vs 23.4±8.2 µg/L, P<0.01 or P < 0.05). The fecal IgA and sIgA were not correlated with serum IgA and sIgA, and serum IgA was not correlated with serum sIgA (P >0.05). In patients with CH, CSH and LC, serum sIgA was significantly correlated with alkaline phosphatase (r = 0.523 0, P < 0.01) and total bilirubin (r = 0.4 581, P < 0.01). In patients with AH, serum sIgA level was correlated with alanine aminotransferase (r = 0.4 692, P < 0.01), total bilirubin (r = 0.4 265, P < 0.01).

CONCLUSION: The detection of IgA and sIgA can be used in the clinical diagnosis of hepatic diseases.

Key Words: IgA; sIgA; Hepatic disease

0 引言

肠黏膜sIgA是肠道主要的免疫球蛋白, 是肠道的第一线的免疫防御, 对黏膜固有的和入侵的病原体具有抵抗作用. 我们检测168例各型肝炎和肝硬化患者血清和粪便中IgA和sIgA的含量, 以探讨在各种肝病患者肠道免疫防御的变化情况.

1 材料和方法

1.1 材料

住院肝病患者168例, 男123例, 女45例, 年龄17-94岁, 急性肝炎(包括甲、乙、丙、戊)35例, 慢性重症肝炎9例, 慢性肝炎(包括乙、丙)67例, 肝硬化(包括肝炎后肝硬化和酒精性肝硬化)57例. 粪便正常对照组为我院五官科住院患者(肝功能正常, HBV和HCV血清标志物阴性)30例, 血清正常对照组为我院体检中心健康者(肝功能正常, HBV和HCV血清标志物阴性)50例. 取患者清晨第一次新鲜粪便称质重, 按1︰10(m/m)加入0.01 mol/L pH7.4 PBS, 对照组粪便按1︰2加入0.01 mol/L pH7.4 PBS, 混匀, 漩涡振荡器充分震荡5 min, 以10 000 g低温离心30 min, 取上清-30 ℃冰冻保存待用. 全部受检者于清晨空腹抽血, 分离血清-30 ℃冰冻保存.

1.2 方法

IgA, IgG, IgM用免疫散射比浊法检测, 仪器和试剂为库尔特公司提供, 血清正常参考值分别为IgA 1.0-3.2 g/L, IgG 7.0-15.2 g/L, IgM 0.4-1.6 g/L; sIgA用中国原子能科学院提供sIgA放射免疫分析药盒, 检测仪器为美国德普γ计数器, 按说明书操作; 碱性磷酸酶(ALP)、丙氨酸氨基转移酶(ALT)、总胆红素(T-BIL)分别用优化速率法、连续监测法和亚硝酸盐法, 采用日本日立公司生产7600全自动生化分析仪操作, 正常参考值分别为ALP 750-2 200 nkat/L、ALT 83-667 nkat/L、T-BIL 1.7-20.5 µmol/L.

统计学处理 采用SPSS10.0进行统计学分析, 以P<0.05时有显著性差异.

2 结果

肝病患者粪中IgA和sIgA含量均明显高于正常对照组(P<0.01), 其增高幅度随病变严重程度而增高(表1), 总IgA和sIgA呈显著正相关(r = 0.4371, P<0.01). 肝病患者血清中IgA和sIgA含量均明显高于正常对照组(P<0.01)(表2). 粪中IgA和sIgA与血清中IgA,sIgA含量无相关性(r = 0.1547, r = 0.1593, r = 0.1210, r = 0.1135), 血清中IgA与血清中sIgA亦无相关性(r = 0.1983). 慢性肝炎、慢性重症肝炎、肝硬化患者血清sIgA与ALP(r = 0.5230, P<0.01)、D-BIL(r = 0.458, P<0.01)有相关性; 急性肝炎患者血清sIgA与ALT(r = 0.4692, P<0.01)、D-BIL(r = 0.4265, P<0.01)有相关性.

表1 肝病患者粪便IgA、sIgA含量的变化(mean±SD).

分组	n	IgA(mg/L)	sIgA(mg/L)	ALT(nkat/L)	ALP(nkat)	D-BIL(umol/L)
对照组	30	<67	13±10	260±20	528±43	18±1
重症肝炎	9	251±178b	326±237b	8098±438	3492±510	588±107
肝硬化	57	145±164b	104±109b	5748±342	3151±423	496±189
慢性肝炎	67	80±24b	88±121b	5133±363	2924±445	451±116
急性肝炎	35	100±47b	88±96b	5613±377	3744±362	489±100

表2 肝病患者血清IgA, IgM, IgG, sIgA含量的变化 (mean±SD).

分组	n	IgA(g/L)	IgM(g/L)	IgG(g/L)	sIgA(ug/L)
对照组	50	1.6±0.2	0.8±0.2	8.2±2.4	23.4±8.2
重症肝炎	9	3.4±1.8b	2.0±1.5b	18.7±6.5b	80.3±25.4b
肝硬化	57	4.9±3.3b	1.9±1.2b	19.4±6.7b	50.0±20.5b
慢性肝炎	67	3.3±1.7b	1.5±0.7b	16.3±5.1b	30.5±24.1a
急性肝炎	35	3.1±1.1b	2.1±1.2b	13.1±3.4b	31.1±25.8a

3 讨论

肠道sIgA主要由肠黏膜中的IgA浆细胞分泌出聚合IgA, 然后与上皮细胞分泌的SC结合, 继之被上皮细胞以内化的方式携入胞内形成吞饮小泡, 在小泡内被转运至上皮细胞的顶端, 并以IgA-SC复合物的形式被胞吐释放入肠腔. 血清sIgA的来源有: 一是sIgA直接由胆汁反流入血; 二是肝内膜相SC游离入血后迅速与血中pIgA结合而成. 一般而言, 黏膜病变如炎症、肿瘤只引起局部SC改变, 极少引起大量SC入血, 故血清sIgA多代表肝胆疾病. 人体存在聚和IgA的肠肝循环, 即入血的聚合IgA经肝脏重回肠腔, 因此肝脏是肠道黏膜免疫系统的组成部分. sIgA在肠道免疫中起重要作用, 它能与细菌[1]和病毒[2-4]的特异性抗原相结合或结合在其他毒性分子上, 阻止他们粘附在黏膜表面. 还能排除已穿透上皮细胞层的感染因子, 并与细菌过度生长、细菌易位和肠道渗透性增高呈反比关系[5], 它在抗感染中起重要作用[6,7].

我们发现肝病患者IgA, sIgA显著升高, 随病变严重程度增幅顺序依次为: 重症肝炎、肝硬化、急性肝炎、慢性肝炎, 粪中IgA和sIgA呈显著正相关. 肝硬化等严重肝病时, 内毒素(LPS)产生和吸收增多, 引起内毒素血症, LPS能刺激机体产生抗LPS的抗体[8,9], 用伤寒沙门氏菌通过口腔、鼻腔、直肠和阴道免疫机体发现直肠免疫后, 在结直肠分泌液和粪便内能诱导大量抗LPS-IgA抗体, 此学者认为此菌能进攻不同的黏膜组织, 诱导长期的局部抗LPS的IgA反应[10]. 有学者发现服用适量的LPS后肺合成sIgA以45%增加, 没有任何毒性作用或致热作用[11], 这可能是IgA, sIgA升高的一个原因. 另外活动性肝病时常伴有炎症性肠病、自身免疫性肠病和感染性肠病, 在感染过程中sIgA可升高, 炎症性肠病时B淋巴细胞激活, IgA, IgM, IgG较正常肠黏膜产生更多. 再有在重症肝炎时有抗肝炎病毒的特异性抗体和自身抗体产生, 以及肝库氏细胞功能失调, 失去对肠道抗原的处理能力, 由肠道吸收的细菌抗原及病毒抗原形成的抗体增多. 肝病患者血中IgA, IgG, IgM, sIgA亦显著增高, 血清中sIgA与IgA无相关性, 有学者发现HIV感染者血清中升高的sIgA与血清中的IgA及多聚IgA无相关性, 认为血清中sIgA可能由黏膜部位产生[12]. 本研究结果患者粪中IgA和sIgA与血清中IgA, sIgA也无相关性, 提示血清sIgA与肠道sIgA的合成是相互独立的[13]. 到底血清中sIgA来源于何处有待于进一步探讨. 尽管血清sIgA与IgA无相关性, 但是sIgA与碱性磷酸酶、丙氨酸氨基转移酶、总胆红素呈正相关, 说明sIgA与病变程度有一定的关系, 检测sIgA有助于临床对肝脏病变的鉴别诊断. 由上可知, 检测肝病患者IgA, sIgA对临床诊断有重要意义, 尤其粪便的检测, 由于取材简便, 方便患者, 减少抽血的麻烦, 易于临床应用.

备注

电编:张勇 编辑:潘伯荣 审读:张海宁

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