尿毒癥病患甲型免疫球蛋白低下的研究

【論文類別】畢業(yè)論文

【中文摘要】

感染是尿毒癥病患主要的致死原因的一，而免疫系統(tǒng)的缺失是造成病患增加感染的主因。

本科曾發(fā)現(xiàn)兩位長期血液透析病人患有反復(fù)性皮膚及呼吸道感染，在探求其反復(fù)感染的原

因時(shí)，意外發(fā)現(xiàn)兩位病患均并有甲型免疫球蛋白（IgA）低下的現(xiàn)象。因此本研究的目的即

在篩檢尿毒癥患者發(fā)生血清IgA低下情形，及探討產(chǎn)生IgA缺乏可能的機(jī)轉(zhuǎn)。

首先選取250位正常人、56位慢性腎衰竭但尚未進(jìn)行透析的病患、246位長期血液透析、及

40位腹膜透析病患，測(cè)定上述四群人血清IgG、IgA、IgM以了解尿毒癥病患與正常人的差異

。結(jié)果發(fā)現(xiàn)長期血液透析或腹膜透析病患其血清IgA濃度相較于正常人、慢性腎衰竭病患皆

有明顯的下降（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%）呈現(xiàn)

完全性甲型免疫球蛋白缺乏，但正常人與慢性腎衰竭病患則無此發(fā)現(xiàn)。另有10位血液透析

病患、2位腹膜透析病患、及2位正常人為部分性甲型免疫球蛋白缺乏。

為排除尿毒癥病患血清IgA濃度較低是否因?yàn)檠写嬗心撤N物質(zhì)干擾IgA測(cè)定所致，將正常

人血清與尿毒癥病患血清作不同比例混合重新測(cè)定，結(jié)果發(fā)現(xiàn)并無此干擾現(xiàn)象，顯示尿毒

癥病患血清IgA濃度較低確實(shí)存在。因有報(bào)導(dǎo)指出C型肝炎與IgA缺乏有關(guān)，而尿毒癥病患C

型肝炎的比例又比一般人高，因此我們亦有比較B型肝炎及C型肝炎與IgA缺乏的相關(guān)性。結(jié)

果顯示，尿毒癥病患罹患B型肝炎、C型肝炎與IgA缺乏無關(guān)。而且病患進(jìn)入透析時(shí)間的長短

及肌酐酸濃度亦與IgA濃度無關(guān)。臨床上亦發(fā)現(xiàn)尿毒癥病患罹患IgA低下者其感染率比IgA

正常者為高。

為了解尿毒癥病患IgA低下的原因，我們以免疫擴(kuò)散法（double immunodiffusion method

）及酵素結(jié)合免疫吸附試驗(yàn)（ELISA, enzyme link immunoabsorband assay）探討這些病

患是否存在某些自體抗體；結(jié)果顯示，有3位病患存在有IgG型的自體免疫抗體。另以流體

細(xì)胞測(cè)量儀（Flow cytometry）研究IgA缺乏是否因B淋巴球或制造IgA的B淋巴球低下所導(dǎo)

致；結(jié)果顯示，IgA缺乏的尿毒癥病患其B淋巴球及制造IgA的B淋巴球數(shù)目確有下降的情形

。

因此本研究有下列結(jié)論：1）長期透析的尿毒癥病患血中IgA較正常人為低；2）尿毒癥病

患IgA缺乏的盛行率較一般人及未進(jìn)入透析的慢性腎衰竭病患者高；3）尿毒癥病患患有IgA

缺乏者，其感染率較一般人高，故具有臨床意義；4）尿毒癥病患IgA低下與進(jìn)入透析時(shí)間

，肌酸酐濃度，及B型、C型肝炎無關(guān)；5）尿毒癥病患產(chǎn)生抗IgA自體免疫抗體（IgG 型）

、或B淋巴球及制造IgA的B淋巴球數(shù)目偏低，皆為造成IgA 缺乏的機(jī)轉(zhuǎn)，顯示其機(jī)轉(zhuǎn)并非單

一性

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【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.

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【目錄】

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

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

第一章

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

第二章 尿毒癥病患血清免疫球蛋白的濃度，及甲型免疫球蛋白缺乏的盛行率------------

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

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

二、結(jié)果------------------------------------------------12

第三章 尿毒癥病患假型免疫球蛋白低下的臨床意義----------------14

一、尿毒癥病患甲型免疫球蛋白低下與感染相關(guān)性------------15

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

第四章 尿毒癥病患甲型免疫球蛋白低下原因的探討----------------18

一、干擾因子的測(cè)定--------------------------------------19

二、自體免疫抗體的偵測(cè)----------------------------------20

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

第五章 綜合討論與結(jié)論---------------------------------------- 31

參考文獻(xiàn)------------------------------------------------------36

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