1. Immunodeficiency diseases
Paediatrics teaching ppt
Immunodeficiency diseases
Xinhua Hospital
Shanghai Institute for Pediatric Research
Tong-Xin Chen

2. Development of Immune System
Development of IgG in Newborn Infant
Up to normal adults level
From mother mainly
Achieve to 60% of adults level when 1 year old，and 100% of adults level when 6 years old
IgG could be subdivided into IgG1、IgG2、IgG3 and IgG4
Age dependent changes of serum IgG level synthesized by themselves：IgG1(5y)；IgG3(10y)；IgG2 and IgG4(14y)
新生儿(Neonate)出生后IgG的发生
可达正常成人水平
但自身合成的数量很低，主要是来自母体
1岁时IgG达到成人的60%，6岁时才能达到成人100%的水平。
IgG分为IgG1、IgG2、IgG3和IgG4四个亚类(subclasses)，
自身合成IgG各亚类的发育过程不全相同，达成人水平的年龄为：IgG1为5岁；IgG3在10岁左右；IgG2和IgG4约为14岁

3. Cord blood IgG level ≥ IgG from mother(>10% of IgG from mother )
IgG from mother are catabolized gradually after born
IgG from mother disappeared completely when 6 months , serum IgG levels of 3~6 months infant are lowest ，especially IgG2 and IgG4
脐血IgG等于或稍高于母体水平(超过母体水平10%)
母体IgG出生后逐渐被分解代谢
6个月时母体来源IgG全部消失，因此3~6月龄婴儿血清IgG水平降到最低点，尤其是IgG2和IgG4的含量更低

4. Development of IgM in Newborn Infant
IgM from mother can not pass placenta, serum IgM of fetuses synthesis when born < mg/L
Normal neonatal IgM increase rapidly after born 4-7 days,is likely to be associated with the response of IgM to intestinal bacteria
If increasing，implicating neonates are stimulated by “nonself” antigen in uterus
新生儿出生后IgM的发生
母体的IgM不能通过胎盘，出生时胎儿自身合成的血清IgM含量小于 mg/L
正常新生儿出生4-7天以后IgM迅速上升，可能与肠道细菌抗原刺激导致的IgM免疫应答有关
如果增高，提示新生儿在宫内受到了“非己”抗原的刺激，可能存在着宫内感染(infection)

5. Development of IgA in Newborn Infant
Can not pass placenta, serum IgA level achieve to 20% of adults level when 1 year old，and 100% of adults level when 12 years old
Cord blood IgA level ≤50mg/L，increasing of IgA implicates the possibility of infections in uterus
IgA is detectable in tears and saliva of 2-3 weeks neonate
The biological function of IgA is defend against some local mucous infections
新生儿出生后IgA的发生
不能通过胎盘，1岁时20%，12岁时达成人水平
脐带血IgA很少超过50mg/L，若增高同样提示宫内感染的可能
生后2-3周的婴儿可在眼泪和唾液中检测到IgA
IgA的生物学作用主要是局部粘膜的免疫保护

6. Cellular Immunity of Newborn Infant
Number of T lymphocytes are usually normal
CD4+T cells are relatively higher，CD4/CD8 up to 3~4，consequently, are susceptible to infections
Function of Th2 cells are relatively stronger,are susceptible to allergic diseases
CD45RA+T cells are more，CD45RO+T cells are less
Deficiency of Cytokine ：IFN-γ、IL-4，and so on
新生儿出生时细胞免疫
T细胞总数不少
CD4+T细胞相对较多，CD4/CD8比例高达3~4，因而易患感染
Th2细胞功能相对亢进，易患过敏性疾病
CD45RA+T细胞比例较大，CD45RO+T细胞比例较少
细胞因子产生不足：IFN-γ和IL-4等

7. Immunodeficiency diseases，ID
A group of disorders characterized by an impaired ability to produce normal immune response. Most of these disorders are cased by mutations in genes involved in the development and function of immune organs, cells, and molecules.
免疫缺陷病定义：
是指免疫系统的器官，免疫活性细胞（如淋巴细胞、吞噬细胞）及免疫活性分子（免疫球蛋白、淋巴因子、补体和细胞膜表面分子）发生缺陷引起的某种免疫反应缺失或降低，导致机体防御能力普遍或部分下降的一组临床综合症。
Primary and acquired

8. Classification of Primary Immunodeficiency Diseases(7 main Categories)
Antibody or B cells deficiency（50%）
Combined immunodeficiency（20%）
Phagocytic dysfunction（18%）
Cellular or T cell deficiency （10%）
Complement deficiency （2%）
Immunodeficiency with other important characteristics
Immunodeficiency with or acquired other congenital or hereditary diseases
原发性免疫缺陷病分类（七大类）
以抗体缺陷为主的体液免疫缺陷（50%）
联合免疫缺陷（20%）
吞噬细胞数量和功能缺陷（18%）
以T淋巴细胞缺陷为主的细胞免疫缺陷（10%）
补体缺陷（2%）
免疫缺陷伴其它重要特征
免疫缺陷伴随或继发于其它先天性或遗传性疾病

9. The incidence of PID Calculated by alive infants：1/10000
（Japan 1981 and Australia 1983）
Hongkong report：1/8000
There is no statistics report in mainland so far
According to the incidence of 1/10000，2500/ nerborn infants every year in our country，cases add up to 3~8 ten thousands at least
More than 100 cases in our hospital since 1970
发病率(incidence)
以活产婴计算：1/10000
（1981年日本和1983年澳洲的报道）
香港报道：1/8000
目前我国大陆尚无统计学报道
按1/10000的发病率，我国每年新出生的2500万新生儿中应有2500个，累计病例至少3~8万
我院30年来（1970年）共发现100多例

10. Clinical features Recurrent infection High risk of autoimmune diseases
High risk of malignancy
临床表现（三大症状）
反复感染
自身免疫性疾病 肿瘤

11. Infection Severe infection、 Refractory infection 、
Recurrent infection 、
Opportunistic pathogens infection 、
Recurrent diarrhea、

12. Autoimmunity diseases
Children with immunodeficiency have higher risk of autoimmune than normal(0.01%~14%)
Autoimmunity diseases
Autoimmune disease suspicious
Arthritis
SLE，JRA
Thrombocytopenia
ITP
Neutropenia
Crohn’s desease
SLE
Hemolytic anemia
Immunodeficiency
associated with autoimmune
X-Linked Agammaglobulinemia
Selective IgA Deficiency
CVID
Thymic hypoplasia
Immunodeficiency with hyperIgM
Chronic granulomatosis
Complement deficiency
Wiskott-Aldrich Syndrome
免疫缺陷病患儿发生自身免疫疾病的机会比正常人群高（0.01%~14%）
Autoimmune disease suspicious易伴发的自身免疫性疾病
Common variable Immunodeficiency

13. Children with immunodeficiency have higher risk of cancer than normal(100~300 fold)
Tumor

14. Primary immunodeficiency suspicious
History
Tympanitis more than 8 times per year
Severe nose sinusitis more than 2 times per year
Pneumonia more than 2 times per year
Deep infection in abnormal position more than 2 times
Recurrent infection in deep skin or viscera
Infection eliminated with antibiotics by intravenous injection
Rare or opportunistic pathogens infection
Family PID history
原发性免疫缺陷病预警症状 病史
一年中有8次以上中耳炎,
一年中有2次以上严重鼻窦炎
一年中有2次以上肺炎
在非常见部位发生深部感染2次以上
反复发生深部皮肤或脏器感染
需要应用静注抗生素才能清除感染
非常见或条件性致病菌感染
家庭有PID病史者

15. Clinical features Growth development deficiency
Lymph nodes or tonsil deficiency
Skin changes:capillary vessel expand, petechia
Skin mildew, lupus erythematosus-like tetter
Ataxia(A-T)
Thrush after 1 year old
Oral ulear
生长发育仃滞
缺乏淋巴结或扁桃体
皮肤病变:毛细血管扩张,出血点
皮肤霉菌,红斑性狼瘡样皮疹
共济失调(A-T)
一岁以后出现的鹅口瘡
口腔溃疡

16. Laboratory analysis： Serum IgG，IgM，IgA（B cell function）
CD3，CD4，CD8 （T cell subsets）
CD19（ number of B cell ）
CD56/16（ NK cell ）
White blood cell count or nitroblue tetrazolium（ NBT ）test
Complement
NBT吞噬功能

17. Cytokine： IL-2，IL2R，IFN，IFNR Cell surface molecular：CD18
IgG subclasses（1~4）
Thymus：X -ray
Cytokine： IL-2，IL2R，IFN，IFNR
Cell surface molecular：CD18
Gene analysis：BTK ，CD40L，WASP 

18. Common primary immunodeficiency diseases
Combined immunodeficiency （14）
Antibody or B cells deficiency （10）
Cellular or T cell deficiency （9）
Immunodeficiency with other important characteristics（3）
Phagocytic dysfunction （12）
Complement deficiency （16）
Immunodeficiency with or acquired other congenital or hereditary diseases （41）
几种常见的原发性免疫缺陷病
联合免疫缺陷（14）
以抗体缺陷为主的体液免疫缺陷（10）
以T淋巴细胞缺陷为主的细胞免疫缺陷（9）
免疫缺陷伴其它重要特征（3）
吞噬细胞数量和功能缺陷（12）
补体缺陷（16）
免疫缺陷伴随或继发于其它先天性或遗传性疾病 （41）

19. X-linked agammaglobulinaemia
Selective IgA deficiency
Thymic hypoplasia
Combined immunodeficiency

20. X-linked agammaglobulinaemia （ XLA ）
Also named as Bruton disease（described in 1952）
Discovered that the disease was associated with mutation of the gene coding pre B-cell cytoplasmic tyrosine kinase（ btk）in1993
Mutation lead to block in signal transduction of B cell development，block in maturation after the pre-B cell stage ,lead to decreaseing of mature B cell
The patterns of mutations are diverse，more than 118　cases are reported so far　
X-linked agammaglobulinaemia （ XLA ）
Also named as Bruton disease（discovered in 1952）
1993年发现本病与编码前B细胞胞浆内酪氨酸激酶（pre B-cell cytoplasmic tyrosine kinase，btk）基因突变有关
突变可致B细胞发育的信号传导受到障碍，使B细胞分化受阻，导致成熟B淋巴细胞大量减少
突变的形式多样，目前文献报道有118种以上。

21. Clinical features Male Onset during 4~6 months of age
Recurrent Pyogenic bacterial infection
Respiratorty tract infections are typical，as well as systemic infections
临床特点 男性
4 ~ 6月龄以后起病
反复化脓性细菌性感染
多为呼吸道感染，也有全身感染

22. Immunological characteristics：
Can hardly produce antibody，all kinds of Ig are markedly reduced
IgG < 2g/L ( <200mg/dl )
IgA <0.02g/L ( <2mg/dl )
IgM <0.1g/L ( <10mg/dl )
Circulating B cells are markedly decreased，usually less than 0.5% of total lymphocytes
Numbers and function of T lymphocytes are normal
Btk gene located on Xq is deficiency
免疫学特征：
几乎没有生成抗体的能力，各类免疫球蛋白浓度低下
IgG < 2g/L ( <200mg/dl )
IgA <0.02g/L ( <2mg/dl )
IgM <0.1g/L ( <10mg/dl )
循环B细胞显著，通常占总淋巴细胞0.5%以下
T淋巴细胞细胞的数量和功能均无损
btk基因缺损，基因定位于X染色体长臂Xq 位置

23. Alteration of T cell subsets

24. Alteration of B cell and NK cell

25. Mutation of Btk gene 62145-62155 Exon10F 62155-62145 Exon10R
cDNA mutation:
989_999delTGACTCGGAGTinsGGTGGTATTCCAAA
Codon change:
MTRS286_289RWYSK
Mother status:
carrier
Exon10F
Exon10R

26. Differential diagnosis ：
Characteristics
Age
IgM
IgG
IgA
Molecular deficiency
B cell
IgG replacement?
XLA
congenital（＞6m）
reduced
absent/ reduced
BTK
yes
infantile transient
hypogammaglobulinemia
1~2y
normal
reduced
unclear
presence no
与婴儿暂时性低丙种球蛋白血症鉴别：

27. Common Variable Immunodeficiency （ CVID）
A heterogeneous group of diseases characterized by antibody defects
Late-appearing immunodeficiency
Immunological characteristics of CVID
Antibody deficiency IgG <2.5g/L ( <250mg/dl )
IgA usually is reduced
IgM usually is reduced
Circulating B cells usually are normal or decreased
Cellular immunity：normal or help function deficiency
常见变异型免疫缺陷病:
是一组病因不同的、主要影响抗体合成的PID
是一种迟发性（late-appearing）免疫缺陷病
CVID免疫学特征
抗体形成缺损 IgG <2.5g/L ( <250mg/dl )
IgA 大多数病人也降低
IgM 大多数病人也降低
循环B细胞  往往正常
细胞免疫：正常或缺乏辅助功能

28. Clinical manifestations ：
Recurrent infection （ bacterial infection）with onset at any age, affects both males and females
High risk of gastrointestinal infections，usually chronic giardiasis
Lymphoma and gastric carcinoma occur with increased frequency
Increased incidence of autoimmune disease(hemolytic anemia 、pernicious anemia、 thrombocytopenia,et al)
lymphoproliferation，splenomegalia，lymphoid hyperplasia
临床特点：
起病于任何年龄的反复感染（以细菌感染为主），男女都可发病，
高发胃肠道疾病，常见慢性兰氏贾弟鞭毛虫病。
淋巴网状系统及胃肠道恶性肿瘤
自身免疫病(溶血性贫血、恶性贫血、血小板减少病等)
淋巴增殖病，脾肿大，广泛性淋巴结病(淋巴组织增生)

29. X-linked agammaglobulinaemia
Selective IgA deficiency
Thymic hypoplasia
Combined immunodeficiency

30. Incidence：Caucasian1/500~1500，Japanese1/18500，Chinese1/5000~10000
Associated with maladjustment of Th2 cell to B cell produce IgA
Both males and females, often coincide in same family
Mild form is asymptomatic
Recurrent infections in infancy（respiratory 、intestinal and urinary infections ）
Be associated with autoimmune diseases、asthma and intestinal malabsorption
发病率：白种人1/500~1500，日本人1/18500，中国人1/5000~10000
Th2细胞对B细胞合成IgA调控失调有关
男女均可发病，家族中可数人发病
轻症无症状
婴儿期发生反复感染（呼吸道、肠道和泌尿道）
可伴发自身免疫性疾病、哮喘和肠道吸收不良

31. Serum IgA less than 0.05g/L，IgM、IgG normal or increased
sIgA markedly reduced
Serum IgA could increase to normal level in some cases
Should not be treated with IVIG，since capable of forming anti-IgA antibodys subsequent allergy
血清IgA低于0.05g/L，IgM、IgG正常或升高
分泌型IgA明显减少
部分病例血清IgA可逐渐升至正常水平
应避免使用IVIG，易产生抗IgA抗体而发生过敏反应

32. X-linked agammaglobulinaemia
Selective IgA deficiency
Thymic hypoplasia
Combined immunodeficiency

33. Thymic hypoplasia also is called DiGeorge syndrome（1964年）
It is known now that 80%~90% Digeorge syndrome have minor deletion of gene located at 22q11
Minor deletion of gene located at 22q11 included a group of disease，now called CATCH22 syndrome
胸腺发育不全又称DiGeorge 综合征（1964年）
目前已知80%~90%的Digeorge综合征存在着染色体22q11的微基因缺失
染色体22q11的微基因缺失可包括一组疾病，目前称之为CATCH22综合征

34. CATCH 22 Cardiac defects Abnormal facies Thymus hypoplasia
Cleft palate
Hypocalcemia
CATCH 22（取共同的病损首位字母）
心脏缺陷
面容异常
胸腺发育不良 腭裂
低血钙

35. Clinical features： T cell reduced Cardiac defects Abnormal facies
Thymus hypoplasia
Parathyroid hypoplasia
Ⅲ-Ⅳpharyngeal arch hypoplasia
Ⅰ-Ⅱpharyngeal arch hypoplasia
T cell reduced
Cardiac defects
Abnormal facies
Hypocalcemia
主要表现（四大临床症状）：
法乐四联征和大血管异常（如主动脉弓中断等）
Recurrent infections（virus infections ）
Tetralogy of Fallot and aorta abnormal（eg.arcus aortae break off）
Cleft palate 、short philtrum and low-set ears
Tetany

36. Laboratory analysis ：
Number of peripheral blood lymphocytes reduced（<1000个/mm2）
CD3+T cell markedly reduced
Serum Ig normal or reduced，whereas IgE increased
Serum calcium reduced ， serum phosphorus increased ， parathyroidhormone reduced
Chest radiograph: thymus absence
实验室检查：
外周血淋巴细胞计数减少（即<1000个/mm2）
CD3+T淋巴细胞减少明显
血清免疫球蛋白正常或减少，而IgE生高
血钙降低，血磷生高，甲状旁腺素也降低
胸部X线片检查胸腺影缺如。

37. DiGeorge syndrome: Boy 14months Immunodeficiency Hypocalcemia
Bronchopneumonia
Congenital heart disease
Immunodeficiency
Hypocalcemia
Nearside facial paralysis
左侧面瘫

38. Normal Thymus
Thymus shadow of infant(<6m) is visible ，usually>10g
If invisible(< 4g )，implicated thymus hypoplasia
6个月以内的婴儿看到胸腺阴影，一般在10g以上
看不到阴影，多在4g以内预示胸腺发育不良

39. DiGeorge syndrome
Thymus absence

40. X-linked agammaglobulinaemia
Selective IgA deficiency
Thymic hypoplasia
Combined immunodeficiency

41. A group of diseases，occurs both males and females in autosomal recessive SCID，only males in X-linked recessive SCID
Recurrent infections with fungi, bacteria, virus, mycobacterium, protozoa
Typical features: chronic diarrhea、pneumonia and persistent fungal infections （especially thrush）
Sometimes morbilliform rash is the only symptom of SCID in neonatal period ，may caused by GVHR
Usually succumb to overwhelming infection whithin the first year of life
一组疾病，常染色体隐性遗传的SCID男女均可发病，而X性连锁遗传的SCID仅见于男性。
临床表现早期反复、严重霉菌，细菌和病毒感染
最常见的症状表现为难治性腹泻、肺炎和持续性霉菌感染（特别是鹅口疮）
有时新生儿期麻疹样皮疹可能是SCID的唯一症状，其原因可能与轻微移植物抗宿主反应（graft versus host reaction,GVHR）
多在1岁内死于严重感染

42. T- B+NK-Ig- Severe combined immunodeficiency （ SCID）
Approximately 50%~60% SCID are X-linked forms ，the most common genetics alteration is mutation of receptor c of IL-2、IL-4、IL-7、IL-9 and IL-15
Autosomal recessive SCID usually have JAK3 gene deficiency,JAK3 coded a tyrosine protein kinase which is associated with signal transduction initiated by c
严重联合免疫缺陷
X性连锁遗传的SCID约占总病例的50%~60%，最常见的遗传学改变为细胞因子IL-2、IL-4、IL-7、IL-9和IL-15所共有的受体链（c）发生突变。
常染色体隐性遗传的SCID往往有JAK3基因缺陷。由于JAK3可编码一种酪氨酸蛋白激酶，以参与c所启始的信号传递，

43. T- B-NK+Ig-
Autosomal recessive SCID may have mutations of RAG-1 and RAG-2，affects antigen receptor on T、B cells surface
In addition， approximately 50% autosomal recessive SCID have adenosine deaminase （ADA）deficiency
常染色体隐性遗传的SCID还可以有重组酶活化基因（RAG-1和RAG-2）的突变，从而导致T、B细胞表面的抗原受体形成障碍
此外，约50%的常染色体隐性遗传的SCID还可以表现为腺苷脱氨酶（ADA）的缺陷

44. Figure 8 photo of a patient with SCID : candida albicans in the mouth
Boy ，8months
Recurrent pneumonia、thrush
One of his uncle died at 6months unknown cause
T-B+NK-Ig ↓
一个舅舅出生后6mo不明原因死亡
Figure 8 photo of a patient with SCID : candida albicans in the mouth

45. Boy ，4.5months
Fever ，pneumonia，hepatosplenomegaly ，Have abscess after inoculating BCG vaccine 3 months ，rash and diarrhea after transfusion
Figure 8-2 photo of a patient with SCID : GVHD and BCG vaccination

46. Alteration of T cell subsets

47. Alteration of B cell and NK cell

48. Molecular Diagnosis of X-SCID in Patient 1 IL2RG gene PCR direct sequencing
487bp deletion
Deletion mutation from intron 6 to 7 including exon 7 and 2 primer site (IVS6-71 to IVS7-11del487)
Predicted frameshift start at arginine 285 with stop codon (TAA)created at position 342, predicted premature termination (R285fsX342) 
Patient 1: deletion between Intron 6 and intron 7  
Deletion in patient
Deletion in patient  
IVS6-17
IVS7-11
Normal control: Intron 6
Normal control: Intron 7

49. Carrier diagnosis in IL2RG deletion (XSCID) – Patient 1 PCR-agarose gel electrophoresis
Primer Pair
Exon 6F/8R
Exon 5F/8R
-ve control
Patient
Mother
Normal
Causative gene: IL2RG in X-chromosome
PCR amplified for each exon for sequencing
No PCR product for amplification of exon 6, 7 and 8
Suspected large deletion, try other primer pairs combination
Deletion mutation including exon 7 and 2 primer site found (IVS6-71 to IVS7-11del487)
Mother diagnosed as heterozygous carrier by PCR directly

50. T+CD40L-B+IgM↑IgG↓ Hyper IgM syndrome （ HIGM）
Four types，most common type is X-linked form (Hyper IgM syndrome typeⅠ)
Approximately 70%，caused by mutations of the CD40L gene
Diagnosis: CD40L expression on T cell reduced in vitro lymphocyte cultivation
伴高IgM的免疫球蛋白缺乏症
分四型，最常见为X性连锁遗传，即Ⅰ型
占70%，T细胞表面(on T cell surface )CD40L基因突变所致
体外淋巴细胞培养T细胞表达CD40L减少是诊断的要点之一

51. Extracellular pathogens Introcellular pathogens
T-B cell interaction
Infections
IgM
B cell
T cell
Isotype switching
IgG
IgA
IgE
Extracellular pathogens
CD40
MHC-Ag
CD40L
TCR
cytokine
IL-2
IFN-γ
Introcellular pathogens

52. CD40L
patient
control
Fig1. CD40 ligand expression induced by PMA+IM in paitent with HIGM

53. CD40 ligand gene mutations identified in this study
Exon5
cDNA mutation:
 delCTCA
Codon change:
 L205fsX240
Mother status:
 not carrier

54. Laboratory features of some primary Tcell immunodeficiency
Phenotype
Circulating lymphocyte
Serum Ig
Immunodeficiency
SCID
X-linked or JAK3 deficiency
RAG-1 or RAG-2 deficiency
Omenn‘s syndrome
ADA deficiency
ZAP-70 deficiency
Ⅱnake lymphocyte syndrome
Combined T cell and B cell deficiency
PNP deficiency
Ataxia-telangiectasia
Wiskott-Aldrich Syndrome
Selective T cell deficiency
DiGeorge Syndrome T - ↓ +
CD4 - ↓ +
CD8 - ↓ + B ↑ - + NK - +
IgG - ↓
IgG2 ↓ +
IgM ↓ - +
IgA - + ↓ ↑
IgE - ↑ ↓ +
Total number ↓ - +
湿疹-血小板减少伴免疫缺陷(immunodeficiency with eczema and thrombocytopenia)

55. Wiskott Aldrich Syndrome Patient Photo
thrombocytopenic purpura
eczema

56. Ataxia-telangiectasia Patient Photo
患儿的外观形态
眼部球结膜毛细血管扩张
Conjunctiva telangiectasia
Appearance of this patient

57. Treatment ： General management
Strengthen publicizing and nursing，prevent infections
Antibiotics
Specific treatment：thrombocyte for WAS，calcium and Vit D for thymic hypoplasia
Avoid live vaccines to patients with T cell deficiency
Avoid fresh blood productions transfusion to patients with T cell deficiency in case of GVHR，if necessary，should be treated by ray（2000~3000rad）
Screen CMV strictly in blood productions， avoiding CMV infections
加强宣传与护理，预防感染
感染时应用合适的抗生素治疗
对症治疗：WAS给于血小板，胸腺发育不全给于钙剂和Vit D，
T细胞缺陷患儿禁种活疫苗
T细胞缺陷患儿不宜输新鲜血制品，防止发生GVHR，必需时，应先用射线（2000~3000rad）处理
血制品应严格筛查CMV，以防血源性CMV感染

58. Specific treatment to immunodeficiency
B cell deficiency： IVIG
T cell deficiency ： Thymic hormones ， stem cell transplantation
Phagocytic dysfunction ：stem cell transplantation
Complement deficiency ： Replacement therapy ： plasma
Gene therapy ：ADA，SCID （11cases）
免疫缺陷对症治疗
B 细胞缺陷： IVIG
T 细胞缺陷：胸腺素，造血干细胞移植
吞噬细胞功能缺陷：造血干细胞移植
补体缺陷： 替补疗法： 血浆
基因治疗：ADA，SCID （11例）

59. Replacement therapy IVIG replacement therapy ：
80% patients have different degree IgG or other antibodys deficiency
400mg/kg/m
Serum IgG should be increased more than 5g/L in principle
Side effect:anaphylaxis、blood transmitted diseases 

60. Enzyme replacement ：
ADA-PEG：15~30u/ug 1~2/week，subcutaneous injection
Washing erythrocytes for PNP、ADA
Cytokine：
IL-2 for SCID

61. Immune reconstitution
Bone marrow transplantation
Allogenetic homozygote bone marrow transplantation （HLA completely matching）
Allogenetic hemizygote bone marrow transplantation （HLA half matching）
Unrelated donor bone marrow transplantation
骨髓移植
同种异体?同型合子骨髓移植（HLA型完全一致）
同种异体半合子骨髓移植（HLA半匹配）
无关供体骨髓移植

62. Stem cell transplantation （pure stem cell CD34+）
Cord blood stem cell transplantation
Peripheral blood stem cell transplantation
Thymus transplantation
<16week fetal thymus transplantation
Apply to cellular immunity deficiency，mostly thymic hypoplasia
胸腺组织移植
<16周的胚胎胸腺植入腹膜下或皮下
应用于细胞免疫缺陷，主要是胸腺发育不全 

63. Gene therapy Mutant gene Clone  identify location of mutation
Gene transformation
Target gene fragment stem cell genome of patients
Transgenic cell mitosis，
gene transformation fragment replicate
insert
突变基因
克隆  确定突变位置
基因转化
目的基因片段 患者干细胞基因组
转基因细胞有丝分裂，
转化的基因片段复制

64. Effect of gene therapy：
ADA
XL-SCID （11cases）
ZAP70
JAK3
LAD
WAS
PNP
MHC II
CGD
XLA
good
bad
uncertainty

66. Thank you!