尿毒症病患甲型免疫球蛋白低下的研究

【论文类别】毕业论文

【中文摘要】

感染是尿毒症病患主要的致死原因的一，而免疫系统的缺失是造成病患增加感染的主因。

本科曾发现两位长期血液透析病人患有反复性皮肤及呼吸道感染，在探求其反复感染的原

因时，意外发现两位病患均并有甲型免疫球蛋白（IgA）低下的现象。因此本研究的目的即

在筛检尿毒症患者发生血清IgA低下情形，及探讨产生IgA缺乏可能的机转。

首先选取250位正常人、56位慢性肾衰竭但尚未进行透析的病患、246位长期血液透析、及

40位腹膜透析病患，测定上述四群人血清IgG、IgA、IgM以了解尿毒症病患与正常人的差异

。结果发现长期血液透析或腹膜透析病患其血清IgA浓度相较于正常人、慢性肾衰竭病患皆

有明显的下降（225 ±100 mg/dl、217 ±97 mg/dl vs. 270 ±96mg/dl、296 ±137 mg/

dl，p < 0.0001, ANOVA）。4位血液透析病患（1.63%）及1位腹膜透析病患（2.5%）呈现

完全性甲型免疫球蛋白缺乏，但正常人与慢性肾衰竭病患则无此发现。另有10位血液透析

病患、2位腹膜透析病患、及2位正常人为部分性甲型免疫球蛋白缺乏。

为排除尿毒症病患血清IgA浓度较低是否因为血中存有某种物质干扰IgA测定所致，将正常

人血清与尿毒症病患血清作不同比例混合重新测定，结果发现并无此干扰现象，显示尿毒

症病患血清IgA浓度较低确实存在。因有报导指出C型肝炎与IgA缺乏有关，而尿毒症病患C

型肝炎的比例又比一般人高，因此我们亦有比较B型肝炎及C型肝炎与IgA缺乏的相关性。结

果显示，尿毒症病患罹患B型肝炎、C型肝炎与IgA缺乏无关。而且病患进入透析时间的长短

及肌酐酸浓度亦与IgA浓度无关。临床上亦发现尿毒症病患罹患IgA低下者其感染率比IgA

正常者为高。

为了解尿毒症病患IgA低下的原因，我们以免疫扩散法（double immunodiffusion method

）及酵素结合免疫吸附试验（ELISA, enzyme link immunoabsorband assay）探讨这些病

患是否存在某些自体抗体；结果显示，有3位病患存在有IgG型的自体免疫抗体。另以流体

细胞测量仪（Flow cytometry）研究IgA缺乏是否因B淋巴球或制造IgA的B淋巴球低下所导

致；结果显示，IgA缺乏的尿毒症病患其B淋巴球及制造IgA的B淋巴球数目确有下降的情形

。

因此本研究有下列结论：1）长期透析的尿毒症病患血中IgA较正常人为低；2）尿毒症病

患IgA缺乏的盛行率较一般人及未进入透析的慢性肾衰竭病患者高；3）尿毒症病患患有IgA

缺乏者，其感染率较一般人高，故具有临床意义；4）尿毒症病患IgA低下与进入透析时间

，肌酸酐浓度，及B型、C型肝炎无关；5）尿毒症病患产生抗IgA自体免疫抗体（IgG 型）

、或B淋巴球及制造IgA的B淋巴球数目偏低，皆为造成IgA 缺乏的机转，显示其机转并非单

一性

--------------------------------------------------------------------------------

【英文摘要】

Infection is one of the major causes of mortality and morbidity in uremic

patients. Impaired host defense is the important predisposing factor. We

experienced two hemodialysis (HD) patients with recurrent skin and

respiratory

tract infections in 1992 and 1995. Unexpectedly, we found both of them

were

IgA deficiency (IgAD). Therefore, we conducted the following studies to

survey

the prevalence and the mechanisms of IgAD in uremic patients. Serum

Immunoglobulin (Ig) G/A/M concentrations of 246 HD, 40 continuous

ambulatory

peritoneal dialysis (CAPD), 56 chronic renal failure (CRF) patients, and

250

normal controls were examined by Nephelometry. Lower serum IgA

concentrations

were found in HD and CAPD patients in comparison to normal controls and

CRF

patients ( 225 ±100 mg/dl, 217 ±97 mg/dl vs. 270 ±96 mg/dl, 296 ±137 mg/

dl; p<0.0001, ANOVA). Four HD patients (4/246, 1.63%) and one CAPD (1/40,

2.

5%) were found to be completely IgA deficient (IgA < 6.65 mg/dl). However,

there was no such finding in CRF and normal groups. Partial IgAD were

found in

10 HD patients, 2 CAPD patients and 2 of controls.

The possibility of uremic toxin interfering with the measurement of IgA by

nephelometry was excluded by serial dilution of patient's serum mixing

with

serum of normal control. The decrease of serum IgA concentrations did not

correlated with serum creatinine concentrations, nor with the HD duration.

There was no association between IgA deficiency and hepatitis B or C. To

explore the mechanisms of IgAD, the presence of anti-IgA antibody in

patient's

serum was detected by double immunodiffusion and enzyme-linked

immunoabsorbant

assay (ELISA).　And the numbers the B cell and IgA secreting B cell were

studied by Flow cytometry to know whether the IgAD was caused by

impairment of

IgA production. ELISA revealed positive result in 3 cases of IgAD, which

indicated the presence of IgG type anti-IgA autoantibody. By Flow

cytometry,

decreased numbers of B cell and IgA secreting B cell were detected.

In conclusion, the results showed 1) Serum IgA concentrations were lower

in

both HD and CAPD patients. 2) A higher prevalence of selective IgA

deficiency

in dialysis patients. 3) The clinical symptoms were more obvious in uremic

patients with IgAD, so the deficiency of serum IgA in uremic patients has

the

clinical significance. 4) Decreased serum IgA concentration in uremic

patients

was not related to the dialysis duration, serum creatinine level, and the

existence of hepatitis B or C. 5) Some of the uremic patients with IgAD

were

caused by the existence of circulating anti-IgA autoantibody, but some

were

caused by decrease of the numbers of B cell and IgA secreting B cell,

which

indicate that the mechanisms of IgA deficiency in uremic patients are

diversified.

--------------------------------------------------------------------------------

【目录】

中文摘要------------------------------------------------------ 3

英文摘要-------------------------------------------------------5

第一章

前言------------------------------------------------7

第二章 尿毒症病患血清免疫球蛋白的浓度，及甲型免疫球蛋白缺乏的盛行率------------

----------------------------------------------9

一、方法及材料------------------------------------------10

二、结果------------------------------------------------12

第三章 尿毒症病患假型免疫球蛋白低下的临床意义----------------14

一、尿毒症病患甲型免疫球蛋白低下与感染相关性------------15

二、唾液的甲型免疫球蛋白的探讨--------------------------17

第四章 尿毒症病患甲型免疫球蛋白低下原因的探讨----------------18

一、干扰因子的测定--------------------------------------19

二、自体免疫抗体的侦测----------------------------------20

三、IgA制造功能的探讨-----------------------------------25

第五章 综合讨论与结论---------------------------------------- 31

参考文献------------------------------------------------------36

表------------------------------------------------------------41