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Serodiagnosis of viral
infection
How to identify an unknown virus
infection?
Virus isolation and identification (sometime
danger and not easy)
PCR or RT-PCR
Antibody screening
Significance of antibody against
virus
Protective, such as anti-HBsAb
Infected, such as anti-HCV, anti-HIV
Why?
Home work: please search medline, find out the
original papers and describe how HCV and HIV
were identified to be associated with post
transfusion hepatitis and AIDS, respectively.
Outline
Epstein-Barr Virus (EBV)
Hepatitis virus (HAV, HBV, HCV)
Human Immunodeficiency Virus (HIV)
Epstein-Barr Virus (EBV)
1932年Paul跟Bunnell發現infectious mononucleosis
(IM)患者的heterophil antibody效價顯著增高
1964年Epstein由Burkitt’s Lymphoma中發現病毒,便
取名為Epstein-Barr Virus(EBV)
Epidemiology
世界各地分布極廣,經常感染兒童,尤其是落後地區
兒童血清EBV抗體陽性反應高達80%
兒童感染EBV通常無臨床症狀,僅出現fever或輕微
上呼吸道症狀
青少年或成人感染則易出現infectious
mononucleosis (IM)為一種急性或亞急性.良性.具
傳染性之淋巴球增生疾病,好發於年輕人
主要傳播途徑-saliva
口腔上皮細胞有EBV receptor--CD21(又稱為CR2)
EBV病毒特性
屬於herpes virus
病毒大小150-200nm
Double strand DNA
有capsid也有envelope
病毒複製時最早出現抗原為EBNA、EMA,之
後出現兩種EA
最後出現VCA、LMA
EBV
Specific antibody responses in IM
Anti-VCA IgM用來診斷IM具有良好特異性
Anti-EBNA則可視為曾經感染EBV的指標
EBV-Associated Tumors
Burkitt’s lymphoma(BL) :散佈世界各地,但
以非洲瘧疾流行區域最多
好發於3-15歲兒童,6-7歲發生率最高
100%具有對EBV的抗體,其中以anti-VCA
比一般對照血清的平均值高8-10倍
鼻咽癌NPC
為一種惡性鱗狀上皮細胞腫瘤
anti-VCA IgA 比一般對照血清平均值高10
倍
anti-EA/D也會升高EA/R則否
anti-VCA和anti-EA/D兩者與腫瘤體積有關,
能作為預後的指標
Laboratory diagnosis
發病2-3週間肝臟酵素會上升;30%患者膽紅素
會上升3-8mg/dL
血清檢查分兩大類:
1.specific antibody測定
2.heterophil antibody測定
小於4歲兒童有70-80 %嗜異型抗體呈陰性反應,
故幼童檢查必須測定專一性抗體
IM患者有85%會呈現嗜異型抗體positive,若為
negative則可能為CMV或其他如rubella、
toxoplasma、adenovirus所引起
Hematologic examination
IM患者有3%為coomb’s test positive
淋巴球總數比常人多(≧50%) ,主要為atypical
lymphocyte增加(≧10%)
EBV只感染B淋巴球 ,但是B、T淋巴球皆會因
EBV感染而變成atypical lymphocyte (T淋巴球是
因為病毒抗原或B淋巴球抗原而產生的免疫反
應)
Serologic test of EBV-specific antibodies
檢anti-VCA或anti-EA可採用間接免疫螢光分析
法,測定anti-EBNA則市採用抗補體間接免疫
螢光法
P3HR-1可用來測定anti-VCA IgG、IgA、IgM
Raji細胞株用於EBNA的測定
EA測定必須將病毒細胞株以sodium butyrate、
halogenated pyrimidines或腫瘤促進因子處理,
使EBV表現EA抗原
EBV感染之血清反應
判讀
抗體種類
Anti-VCA
IgM
Anti-VCA
IgG
Anti-EA
AntiEBNA
PB
-
+
±或-
-
+
+
-
±或-
±或-
-
-
±或-
-
+
-
過去曾感
染
-
+
-
+
-
過去曾感
染,可能
再度活化
-
+
±或-
+
-
無感染
急性感染
最近曾感
染
heterophile antibody
IM的heterophile antibody又稱為Paul-Bunnell
antibody
其他抗體
(1)serum sickness antibodies:注射過馬血 清會出現
的heterophil antibody
(2)forssman antibody:天竺鼠腎臟物質免疫動物所
引出的抗體
heterophile antibody被不同細胞抗原所吸附的
情形
抗體來源
綿羊RBC 馬RBC
牛RBC
天築鼠腎
臟
IM
+
+
+
-
Serum
sickness
+
+
+
+
Forssmanindused
+
+
-
+
各種 heterophile Ab TEST
Paul-Bunnell test
Davidsohn-differetial test
Monospot test
Paul-Bunnell presumptive test
Absorbed Heterophile Test
(Davidsohn Differential)
EB capsid Ab (IgM)
目的
原理
測定血清中EBV VCA抗原之IgM抗體,為EBV正在感染的指標
方法
1. Serum以RF吸收劑做1:10稀釋,讓RF吸收劑作用15mins
2. 滴片,37 ℃放置90mins
3. PBS wash,泡在PBS震盪5mins,將slide吹乾
4. 加conjugate, 37 ℃反應30mins
5. 同步驟3.
6. 封片,螢光顯微鏡觀察
應用
EBV VCA IgM代表急性感染的抗體,不須依賴傳染性單核球增
多症狀(IM),即可判斷EBV感染。因幼兒感染EBV通常不會
出現明顯的症狀及嗜異性抗體。
IFA- 抗原: 分泌EBV的Burkitt‘s lymphima之HR1 cell
Ab 1: serum中任何EBV VCA之IgM
Ab 2: FITC conjugated anti-human IgM
EB capsid Ab (IgG)
目的
原理
測定血清中EBV VCA抗原之IgG抗體,為EBV感染的指標
方法
1. Serum作序列稀釋
2. 滴片,室溫放置30mins
3. PBS wash,泡在PBS震盪5mins,將slide吹乾
4. 加conjugate, 室溫反應30mins
5. 同步驟3.
6. 封片,螢光顯微鏡觀察
應用
當傳染性單核球增多症發病後,VCA IgG效價會保持在高效價達
數月之久,而後逐漸下降,並持續終生存在低效價。EBV高效
價抗體常見於布氏淋巴瘤(Burkitt’s lymphoma)、鼻咽癌及免
疫控制的病患。
IFA- 抗原: 分泌EBV的Burkitt‘s lymphima之HR1 cell
Ab 1: serum中任何EBV VCA之IgG
Ab 2: FITC conjugated anti-human IgG
EB capsid Ab (IgA)
目的
原理
測定血清中EBV VCA抗原之IgM抗體,為EBV正在感染的指標
方法
1. Serum與RF吸收劑作用15mins,再作序列稀釋
2. 滴片,37 ℃放置90mins
3. PBS wash,泡在PBS震盪5mins,將slide吹乾
4. 加conjugate, 37 ℃反應30mins
5. 同步驟3.
6. 封片,螢光顯微鏡觀察
應用
研究報告指出:大多數的NPC患者腫瘤增大時 EBV VCA IgA抗
體也會增加,此抗體可當作預後的指標。
IFA- 抗原: 分泌EBV的Burkitt‘s lymphima之HR1 cell
Ab 1: serum中任何EBV VCA之IgA
Ab 2: FITC conjugated anti-human IgA
Hepatitis
Outline
The causative agent of hepatitis
Clinical manifestation/Pathology
Immunology of hepatitis infections
Laboratory diagnosis
Immunization
Hepatitis A Virus
Piconavirus
Enterovirus 72
Known as infectious/epidemic hepatitis
Naked icosahedral capsid, positive-sense,
single-stranded RNA
Pathology
Fecal-oral route
Viral is shed in large quantity into the stool
Can’t initiate chronic infection
Not associated with hepatic cancer
Antibody protection against reinfection is
lifelong
Clinical manifestation
Flu-like: fatigue, nausea, fever
Jaundice (icterus):Yellow eyes and skin
abdominal pain, loss of appetite, diarrhea
average incubation period : 28 days (range: 15
-50 days)
Laboratory diagnosis
ALT and AST :20- to 50-fold
elevations ;ALT/AST (De Ritis) ratio>1
Clinical syndrome
Serology :ELISA or RIA or Competitive
immunoassay
anti-HAV IgM =>recent infection
anti-HAV IgG =>previous infection
Immunization
Inactivated HAV vaccine : Havrix & Vaqta ,only
one serotype, infects only humans=>help ensure
the success of immunization program
Prophylaxis with serum immunoglobulin :80 to 90%
effective in preventing clinical syndrome
Recommended dosages and schedules of hepatitis A vaccines
Vaccine
Havrix
(GlaxoSmithKline)
Vaqta
(Merck & Co.)
Age group
Dose
Volume
# Doses
Schedule
2–18 years
720 El.U.*
0.5 ml
2
0, 6–12 mos.
19 years
and
older
1440 El.U.*
1.0 ml
2
0, 6–12 mos.
2–18 years
25 U**
0.5 ml
2
0, 6–18 mos.
19 years
and
older
50 U**
1.0 ml
2
0, 6–18 mos.
*El.U. = Elisa Units **U = Units
Hepatitis B Virus
Hepadnavirus
Known as serum hepatitis
Enveloped DNA virus, circular, partly doublestranded
Pathology
Transmission
Acute or chronic ,symptomatic or asymptomatic
depend on the person’s immune response
Replicate in the hepatocytes with minimal cytopathic
effect
Cell-mediated immunity and inflammation are
responsible for causing the symptoms and resolution
of the HBV infection by eliminating the infected
hepaocytes
Clinical manifestation
Flu-like: fatigue, nausea, fever
Jaundice (icterus):Yellow eyes and skin
abdominal pain, loss of appetite, diarrhea
average incubation period : (45-160 days)
Laboratory diagnosis
A battery of serological tests are used for the
diagnosis of acute and chronic hepatitis B
infection.
HBsAg - used as a general marker of infection.
HBsAb - used to document recovery and/or
immunity to HBV infection.
anti-HBc IgM - marker of acute infection.
anti-HBc IgG - past or chronic infection.
HBeAg - indicates active replication of virus and
therefore infectiveness.
Anti-HBe - virus no longer replicating. However, the
patient can still be positive for HBsAg which is made
by integrated HBV.
HBV-DNA - indicates active replication of virus,
more accurate than HBeAg especially in cases of
escape mutants. Used mainly for monitoring response
to therapy.
Tests
HBsAg
HBsAb (antiHBs)
HBcAb (antiHBc)
HBsAg
HBsAb (antiHBs)
HBcAb (antiHBc)
Results
Interpretation
Recommendation
negative
Not Immune - has not been
infected, but is still at risk
negative
Get the vaccine.
for possible future infection.
Needs protection.
negative
negative Immune - surface
antibodies present. You may
have been already
The vaccine is
positive vaccinated. Or you have
not needed.
recovered from a prior
negative hepatitis B infection. You
or
cannot infect others.
positive
Tests
Results
HBsAg
positive
HBsAb (antiHBs)
HBcAb (antiHBc)
HBsAg
HBsAb
(anti-HBs)
HBcAb (antiHBc)*
Interpretation
New infection or a
Chronic Carrier negative positive surface antigen,
which means hepatitis B
negative virus is present. You can
spread the virus to others.
or
positive
negative Unclear. Several
different interpretations
are possible. You may
negative need to have these tests
repeated.
positive
*See below.
Recommendation
Find a doctor
who is
knowledgeable
about hepatitis B
for further
evaluation.
The vaccine may
or may not be
needed. Find a
doctor who is
knowledgeable
about hepatitis B
for further
evaluation.
Immunization
HBV vaccine :
subunit vaccine genetically engineered and is
produced by insertion of a plasmid containing
S gene for HBsAg into yeast, Saccbaromyces
cerevisiae
three dose with secondary and third given 1
and 6 months after the first
95% will develop protective antibody
NAME
TYPE VACCINE
COMPANY
STATUS
Hepatitis B Vaccines - Recommended for those at risk and patients with chronic HCV
Engerix B
Recombinant
HBV
GlaxoSmithKline,
Philadelphia, PA
Market, USA
Recombivax HB
Recombinant
HBV
Merck, West Point,
PA
Market, USA
Gen Hevac B
Recombinant
HBV
Aventis Pasteur,
Lyons, France
Market, Europe
Hepacare
(formerly,
Hepagene)
HBV preS1, preS2
PowderJect, Oxford,
Market, Europe
U.K.
Bio-Hep B
HBV S, preS1,
PreS2
Biotech. Gen. Corp.,
Market, Israel
Iselin, N.J.
Hepavax Gene
Recombinant
HBV
Berna Biotech,
Switzerland
Market, Europe
Interferon-α :chronic HBV infection
Hepatitis B immunoglobulin : particular
efficacious within 48 hours of the incident
Limousine/Lamivudine : a nucleoside
analogue reverse transcriptase inhibitor
Hepatitis C Virus
Flavivirus
Known as Non-A, non-B-post-transfusion
hepatitis
Enveloped, positive, single-stranded RNA
Pathology
Transmission :blood ,semen ,vaginal secretion
Liver damage :caused by cell-mediated
immunity
Anti-HCV isn’t protective
immunity to
HCV may not be lifelong
Clinical manifestation
80% of persons have no signs or symptoms.
Flu-like: fatigue, nausea, fever
Jaundice (icterus):Yellow eyes and skin
abdominal pain, loss of appetite, diarrhea
average incubation period : 14-180 days
Laboratory diagnosis
Screening test
Anti-HCV antibodies rise after two months and
are detectable for several years if the patient is
chronically infected.
EIA (Enzyme Immunoassay)
Detect anti-HCV
Sensitivity is highly dependent on the clinical
status
acutely infected nonimmunocompromised
persons :50-70%
chronically infected nonimmunocompromised
persons :97-99%
Laboratory diagnosis
Confirmatory test
NAT (nucleic acid testing )
a. RT-PCR and Branched-chain DNA
b. detect the virus as early as 1~2 weeks after
exposure
c. single positive :confirm HCV infection
d. single negative :not confirm that the patient is not
viremic or has recovered from HCV
RIBA (Recombinant Immunoblot
Assay )
a. 4 recombinant viral proteins on nitrocellulose
strips
b. positive :≧ 2 positive bands
c. Indeterminate :1 positive band
anti-HCV result can’t be determined
Repeat RIBA testing at least 1 month later
d. negative :EIA false positive
Immunization
No vaccine
No post-exposure prophylaxis
Recombinant interferon-α alone or with
ribavirin
Other hepatitis virus
Hepatitis D (HDV):defective RNA virus need
HBV provide envelop, coinfection with HBV or
superinfection with HBV.
Hepatitis E (HEV): similar to HAV in
transmission and clinical course of the disease.
In pregnant women about 10% result in
fulminant hepatitis, detect by PCR or ELISA.
Hepatitis G (HGV): flavivirus-like RNA virus
in hepatitis patients, detected by PCR.
HIV
- HIV structure
- HIV-1 & HIV-2
- Disease
- HIV transmission
- The immunology of HIV infection
- Vaccines
- Laboratory diagnosis
HIV
(human immunodeficiency virus)
Sphere-shaped virus
Lipid envelope
Icosahedral capside
Two copies of linear + ssRNA
Viral protease, reverse transcriptase,
Proviral DNA (provirus)
-ssRNA所反轉錄出的病毒DNA
gag , pol , env
Budding from host cell
integrase
HIV structure
gp41
gp120
p17
p24
Envelope protein: gp120, gp41
Matrix protein: p17
Nucleocapsid structural protein: p24
Bound on RNA: p7, p9
(p7.p9)
HIV genome
gag: p15(p7,p9) , p17 , p24
pol: p31
env:gp120 , gp41
Acquired immunodeficiency
syndrome (AIDS)
後天免疫缺乏症候群主要由HIV-1感染引起 。
HIV-2也會造成AIDS , 但比例相當低 , 3000萬個
case中約600個病人是感染HIV-2 , 主要在西非。
HIV virus 會攻擊CD4 cell , 進而引起免疫低落 , 而
併發其它伺機性感染 , i.e. Kaposis sarcoma
Transmission of HIV
傳染方式:
- Sexual contact (同性.異性)
- Blood or blood product transfusion
- Needle sharing by drug users
- Transplantation of tissues or organs
- Breast feeding (7%)
感染部位:
- M cells: rectal mucosa
- Dendritic cells (i.e. Langerhans’ cells): female
vagina , foreskin epithelia
AIDS
Age vs. HIV infection
HIV infect host cells
宿主細胞種類:
HIV主要攻擊具有表面有CD4分子的細胞
- CD4+ T cells
- Dendritic cells
- Macrophages
- Monocytes
部分HIV會攻擊不具有CD4分子的細胞
- Astrocytes (星狀細胞)
- some epithelial cells
- spermatozoa (經由alternative receptor for gp120)
M-tropic and T-tropic HIV
Course of HIV infection
1. 有明顯的 viremic stage , 且伴隨有類似感冒的症狀 , 約在感
染後數週內 , 此時可偵測到病毒顆粒和病毒RNA。
p24 Ag + , virus culture + , PCR +
2. 空窗期(window period) , 此時病毒Ag titer降低至幾乎消失 ,
只測得到p24 , 且anti-HIV Ab 也還未出現 。
3. Seroconversion , 此時anti-HIV Ab 出現 , 通常感染後2週~6
個月抗體會出現 , Ag下降至測不出 , 難virus culture。
(95%病人會在3~6個月內出現抗體;5%病人在6~18個月時才
出現抗體)
4. 臨床潛隱期(outwardly latent phase) , 這個時期平均約10年,
CD4+ T cell 數量大減 , 可偵測到virus RNA(100%) ,
anti-HIV Ab 高 , 血漿中HIV量低 , 淋巴器官中的HIV高。
Course of HIV infection
5. 伺機性感染和惡性腫瘤期
由於此時的CD4+ T cell數量已下降到極低 , 全身免疫系統已
經被嚴重破壞 , 會造成許多微生物的感染 ,
ex: Candida , CMV , HSV , Mycobacterium tuberculosis 等的感染 。
惡性腫瘤如: Lymphoma , Kaposi’s sarcoma 為最常見的。
此時周邊血液的HIV病毒量上升 , CD4+ T cell 中的proviral
DNA 上升 , anti-HIV Ab 下降。
這一時期可維持數月至數年 , 最後病人死亡。
HIV infection
Vaccines:目前仍在研究階段
Recombinant protein vaccines
-gp120 recombinant protein
-AIDSVAX
-Phase III clinical tirals
-引起anti-HIV Ab反應
-Safe
Attenuated viral vaccines
-Cellular & humoral immunity
-High risk
DNA vaccines
-Using plasmide
-活化特定的B cell , CD4+ T cell , CD8+ T cell
- 反應的量不足以確定後來的保護作用有沒有效
Laboratory diagnosis:
Serological test
先用免疫反應ELISA(or EIA)測定Ab , 再用
western blot test做確定
HIV nucleic acid amplification
Serological Test
大部分方法是檢測 Antibody
檢體收集方法
USA Food and Drug Administration(FDA):
-Urine Based Antibody Tests
-HIV-1 Oral Specimen Collection Device
Urine Based Antibody Tests
Calypte HIV-1 Urine EIA Tests
Enzyme immunoassay (ELISA)
gp160 envelop protein
如果urine檢體結果為positive, 要再使用serum做第
二次的免疫分析
優點:尿液中的HIV不大具有感染性 , 對實驗
室人員來說是一種保護。
目前FDA通過可使用尿液做檢體去測HIV-1的
western blot kit
HIV-1 Oral Specimen
Collection Device
採取檢體後(Ab) , 利用 Oral Fluid Vironostika HIV-1
Microelisa System 或 OraSure HIV-1 Western Blot
kit 檢測
Saliva versus Oral Mucosal
Transudate as Clinical Specimens
是早期使用來避免危害性的檢體收集的方
法
將口水吐到杯子裡
IgA & 少量的IgG
收集效果沒有OraSure device好(因為主要是
檢測IgG)
Serological Test
Anti-HIV antibody detection
(1)Indirect enzyme immunoassay for HIV
(2)Double antigen sandwich assay to detect
anti-HIV antibody
(3)Antibody capture assay for HIV
Western blot
Antigen detection
- Amplification assay
(1) Indirect enzyme immunoassay for
HIV----ELISA
(2) Double antigen sandwich assay to
detect anti-HIV antibody ----EIA
(3)Antibody capture assay for HIV
---ACON
P WP N I
Western Blot
gp160
gp120
當serological screening test 為
positive時 , 使用western blot來
確定IgG Ab 是否對HIV Ag具
有專一性
+: (1)p31 or p24
(2)gp160 or gp120
p66
p55
p51
gp41
p31
p24
p17
p15
I
Antigen detection:
Amplification assay
測Ag,所以在無抗體時期有很高的sensitive
可測定: 突發性感染 , 被針頭刺到的病人 , 先天性
HIV感染(因為母親的Ab只會存在幾個月)
Antibody tests可以無法提供病人作為anti-viral
therapy有效與否的測定 , 因為即使Ag load減低了 ,
Ab 的 titer 仍會一直維持很高。
Antigen detection tests 可用來監測drug
therapy , 但臨床上不夠sensitive , 較常使用
病毒的核酸片段放大。
Antigen detection:
Viral Load Assay
測定serum or plasma中的HIV particles數量
Standard method to monitor anti-viral therapy
可作為突發性感染或是針刺感染的測定 , 以及新生兒HIV
的測定。
(1)the Amplicor HIV-1 Monitor by Roche Diagnostics
(2)HIV-1 QT by Organon Teknika of Merieux SA
(3)HIV-1 RNA 3.0 (Bayer)
HBsAg
HBsAb
HCV Ab
HIV Ab
目的
檢測serum中HBsAg、 HBsAb 、HCV Ab 、HIV Ab的量
原理
Microparticle enzyme immunoassay
方法
1. Analytes bind to microparticles
2. Immune complex binds to glass fiber matrix
3. Conjugate completes the immune complex
4. MUP converts to MU
http://www.abbottdiagnostics.com/Your_Health/Th
yroid/Products/chemimxft3.cfm
應用
HBsAg
HBsAg表面抗原為感染B型肝炎病毒最早出現的血清病毒
標記;急性感染痊癒者,約6個月後產生保護性的表面抗
原抗體(HBsAb)。B型肝炎帶原者未產生HBsAb,其
HBsAg會持續存在。
HBsAb
HBsAb表面抗原抗體具保護力,表示病人對B型肝炎病毒
已具免疫力,可作為施打B型肝炎疫苗成效之評估。
HCV Ab
HCV抗體陽性表示已感染了C型肝炎病毒,此抗體不具保
護力。診斷治療需一併參考臨床表現, C型肝炎為主要之
輸血後肝炎,患者易演變為慢性肝炎及肝癌。
HIV Ab
僅為HIV 抗體篩檢,在感染HIV病毒 4-12週後出現,陽性
反應須再以western blot確認。注意採檢時機,空窗期無法
測得。
CMV
HSV 1&2
Measles
Rubella
目的
檢測CMV、 HSV 1&2 、 Measles、Rubella之IgG或IgM抗體
原理
Ag
酵素免疫法(ELISA)
方法
1. 將serum做稀釋(測IgM要與RF吸收劑作用15mins)
2. Well加入serum,37 ℃放置60mins
3. Wash 4次,加conjugate
4. Wash 4次,加呈色受質溶液
5. 室溫放置30mins,加入終止溶液
6. 1小時內判讀
Human
fibroblast
Monkey
kidney cells
Simian kidney
cells
應用
CMV
1. CMV感染後會終身存在體內,其IgG抗體也終身存在
。篩檢此抗體可減低血清檢驗陰性的受贈者在輸血或
移殖後,感染來自抗體陽性的捐贈者所轉移的病毒。
2. IgM抗體證明最近曾有CMV感染(初次感染或病毒再活
化),可持續12-16週,或依病情而延續表現長達八個月
以上,但並非所有CMV IgM陽性的病毒感染者都有臨
床上的症狀。
HSV 1&2
1. 不是診斷的重要依據,HSV IgG主要是偵測病人體內
HSV的免疫狀況。
2. 近期感染人類單純皰疹病毒(HSV)時,會出現此IgM抗
體,提供診斷治療可減低HSV感染導致腦炎的致死
率。
應用
Measles
1. 麻疹感染後其抗體會終身存在,IgG抗體主要是偵測
病人體內的免疫狀況,因抗體具有保護性,也可作為
施打疫苗成效之評估。
2. 一般出疹後IgM 1-2週才會出現,30-60天後消失。此
IgM抗體陽性表示最近曾感染麻疹病毒。
Rubella
1. 感染出疹後4天,其 IgM抗體會出現,4-6週後消失,
IgM抗體陽性表示最近感染德國麻疹病毒。
2. Rubella IgG主要是偵測病人體內德國麻疹的免疫狀況
,德國麻疹的IgG抗體具有保護性。