vol.9 no.3 september, 2008air.org.tw/air/photo/過敏氣喘通訊vol.9 no.3.pdf · 2019-01-28 ·...

Vol.9 No.3 September, 2008

100 6 5 5081 9 0 8 1 6 6 1

T e l (02) 2311-4670Fax (02) 2311-4732ht tp: / /www.ai r .org. tw

19391392T e l (02) 2311-4670Fax (02) 2311-4732ht tp: / /www.asthma.org. tw

( ----1000-1500 )

Vol.9 No.3 September 2008 1

T ......... 2

................................... 4

( ) ----- .............. 8

(scleroderma) ........................... 9

(Anaphylaxis) ........................ 10

GATA3 .... 14

................................. 15

........................................................... 16

A

1. 10 17 20

FIMSA 10 19

2. 10 19-21

Managing the Spectrum of Symptoms in Upper Respiratory

Disease

3. 97 11 16 ( )14 00-

16 00 9

4. 11 2

5. 11 3 11 30

B

1. 2nd Mediterranean Clinical Immunology Meeting.. October 04,

2008 - October 07, 2008. Turkey. E-mail: immunology@serenas.

com.tr

2. 5th Balkan Meeting of Allergology and Clinical Immunology. Oc-

tober 17, 2008 - October 20, 2008. Greece.

E-mail: [email protected]

3. American College of Allergy, Asthma & Immunology Annual

Meeting 2008. November 07, 2008 - November 12, 2008. United

States. E-mail: [email protected] / [email protected]

4. XXII International Complement Workshop. September 28, 2008 -

October 02, 2008. Switzerland. E-mail: [email protected]

Vol.9 No.3 September 200822222

therapeut ic vacc ina t ion pass ive

immunization passive immunization

T (autologous)

(allogeneic) T

T (adoptive T cell therapy)

[1] 1970 Chester

Southam

leukocytes(autologous leukocytes)

leukocytes

[2]

T

[3]

T (CTL)

T

CD 8+ T T

meta-

static melanoma 20

8

[4]

MART-1-specific CD 8+ T (melanoma-associ-

ated antigen recognized by T cells 1-specific CD8+

T cells)

[5]

MART-1 ?

2

MART-1

[6]

[7]

T

T

T

T

T

T

[8]

T

T

T IL-2

National Cancer Institute

13 progressive metastatic melanoma

cyclophosphamide fludarabine

6 [9] 4

(

)

50% [10]

T

30-40%

T T

[11]

T

melanoma

T

[8]

T

T IL-2

IL-2 T

T

T


EBV-induced lymphoma

EBV-specific T

[12]

T

T

T

T [13]

[14] [15]

[16] T

T TGF-

T [17] T

1. Shankaran, V., et al., IFNgamma and lymphocytesprevent primary tumour development and shapetumour immunogenicity. Nature 410(6832)1107-11, 2001

2. Southam, C.M., et al., Effect of leukocytes ontransplantability of human cancer. Cancer 19(11) 1743-53, 1966

3. Gilboa, E., The makings of a tumor rejectionantigen. Immunity 11(3) 263-70, 1999

4. Yee, C., et al., Adoptive T cell therapy using anti-gen-specific CD8+ T cell clones for the treatmentof patients with metastatic melanoma: in vivopersistence, migration, and antitumor effect oftransferred T cells. Proc Natl Acad Sci USA, 99(25) 16168-73, 2002

5. Yee, C., et al., Melanocyte destruction after anti-gen-specific immunotherapy of melanoma: directevidence of t cell-mediated vitiligo. J Exp Med192(11) 1637-44, 2000

6. Mackensen, A., et al., Phase I study of adoptive T-cell therapy using antigen-specific CD8+ T cellsfor the treatment of patients with metastaticmelanoma. J Clin Oncol 24(31) 5060-9, 2006

7. Marincola, F.M., et al., Escape of human solid tu-

mors from T-cell recognition: molecular mecha-nisms and functional significance. Adv Immunol74 181-273, 2000

8. Galon, J., et al., Type, density, and location of im-mune cells within human colorectal tumors pre-dict clinical outcome. Science 313(5795)1960-4, 2006

9. Therasse, P., et al., New guidelines to evaluatethe response to treatment in solid tumors. Euro-pean Organization for Research and Treatment ofCancer, National Cancer Institute of the UnitedStates, National Cancer Institute of Canada. JNatl Cancer Inst 92(3) 205-16, 2000

10. Dudley, M.E., et al., Adoptive cell transfertherapy following non-myeloablative butlymphodepleting chemotherapy for the treatmentof patients with refractory metastatic melanoma.J Clin Oncol, 2005. 23(10): p. 2346-57.

11. Dudley, M.E., et al., Generation of tumor-infil-trating lymphocyte cultures for use in adoptivetransfer therapy for melanoma patients. JImmunother 26(4) 332-42, 2003

12. Heslop, H.E. and C.M. Rooney, Adoptive cellularimmunotherapy for EBV lymphoproliferativedisease. Immunol Rev 157 217-22, 1997

13. Li, Q., et al., Expanded tumor-reactive CD4+ T-cell responses to human cancers induced by sec-ondary anti-CD3/anti-CD28 activation. ClinCancer Res 5(2) 461-9, 1999

14. Cheever, M.A., et al., Augmentation of the anti-tumor therapeutic efficacy of long-term culturedT lymphocytes by in vivo administration of puri-fied interleukin 2. J Exp Med 155(4) 968-80,1982

15. Chakraborty, M., et al., Irradiation of tumor cellsup-regulates Fas and enhances CTL lytic activityand CTL adoptive immunotherapy. J Immunol170(12) 6338-47, 2003

16. Obeid, M., et al., Calreticulin exposure dictatesthe immunogenicity of cancer cell death. NatMed 13(1) 54-61, 2007

17. Chen, M.L., et al., Regulatory T cells suppresstumor-specific CD8 T cell cytotoxicity throughTGF-beta signals in vivo. Proc Natl Acad Sci U SA 102(2) 419-24, 2005


(Introduction)

( p r i m a r y

immunodeficiencies)

1).

(Medical Therapy of Immune Deficiency)1 1 2

3 3

1 2 3

( )

(Genera l approach fo r d iagnos is o f p r imaryimmunodeficiency) modified from ref. 9.

( )

(General consideration for the treatment of primaryimmunodeficiency) modified from ref. 9.SCID: severe combined immunodeficiencyCVID: combined variable immunodeficiencyBMT/SCT: bone marrow transplant/stem cell transplantIVIG/SCIG: intravernous immunoglobulin/subcutaneousimmunoglobulin

(humoral immunodeficiency), 2).

(cellular immunodeficiency), 3).

(combined immunodeficiency) 4).

(phagocytic defects) 5).

(complement deficiency)

(enzyme) (gene therapy)


(prevention and anticipation)

(severe combined immunodeficiency SCID)

(lymphocyte number)

(in vitro function) T

B natural

killer cells IgG

IgM, IgA

HLA typing(1)

(Avoidance)

(immunocompromised)

(giardia) cryptosporidium

(1)

(Immunoglobulin replacementtherapy)

1952 Dr. Bruton

8 ( X - l i n k e d

agammaglobulinemia)

40 (2)

(IVIG) 1981

( m o r b i l i t y )

(mortality)

(Subcutaneous

IgG SCIG) (9)

(10,11)

400 mg/kg/dose

21-23 3-4

100/kg/dose

CADD-Prizm CADD-Plus infusion pump

20-25 ml/hr( 25 ml)

(trough) IgG 650 mg/dL(

)

IgG 15% (9)

IgA(11)

(selective cel-

lular immunodeficiency) IgA

(IVIG SCIG)

(humoral immune status)(9)

cy tomega lov i rus (CMV)

CytoGam (MedImmune, Inc., Gaithersburg)

- (varicella-zoster) varicella-zoster immune

globulin (VZIG)

ganciclovir (2)

VZIG 96 (1)

(vaccination)

(k i l led or subcomponent

vaccine) (3)

( c o m b i n e d i m m u n e

deficiencies) / /

(measles/mumps/rubella MMR)

(HIV)

IVIG (

) MMR

-

(ataxia-teleangiectasia) DiGeorge


(3)

.

(Antimicrobial treatment)

(therapeutic dose) (4,5,6)

( )Amoxicillin 20 mg/kg/day ( )

Sulfisoxazole 50 mg/kg/day ( )

Trimethoprim-sulfamethoxazole 5 mg/kg/day (

)

Azithromycin 10 mg/kg q week( )

Clarithromycin 7.5 mg/kg/day( )

Amoxicillin-clavulanate 20mg/kg/day (

)

Amoxicillin 500 mg daily 250 to 500 mg bid

( )

Trimethoprim-sulfamethoxazole 160 mg as

trimethoprim daily 80-160 mg bid (

)

Azithromycin 500 mg/kg q wk( )

Clarithromycin 500 mg/day( )

Amoxicillin-clavulanate 875 mg 1000 mg/day

( )

(Primary orsecondary immune deficiency)

(Primary or sec-

ondary immune deficiency)

(mild hypogammaglobulinemia), IgA

IgG (subclass deficiency)(7)

( )

Dr. Barlan 22 IgG3

10 (45.4%)

6.6 1.

3 9.9 1.5 (7)

p n e u m o c y s t i s c a r i n i i

pneumonia(PCP)

(SCID)

(potent immunosuppressive therapy)

IgM (X-linked hyper-IgM syndrome)

PCP

trimethoprim-sulfamethoxazole PCP(8,9)

(Bone marrow transplantor stem cell transplant)

(SCID)

1 HLA-identical related

donor (92.3%)(9)

(reconstitution) .

(PID) (alternative therapy)

( CGD)(9,12)

(Other therapy-enzymes & gene therapy)

autosomal-recessive form

(SCID)

adenosine deaminase defi-

ciency polyethylene glycol-conju-

gated adenosine deaminase 150

2/3 (9)

(X-linked SCID), adenosine deaminase defi-

ciency (X-linked CGD)

(9,13,14)

interferon- - treatment


(thymus transplant)

DiGeorge (9)

(1,8,9)

middle-ear effusion. Pediatrics 71 524, 1983

5. Principi N, Marchisio, Massironii E, et al. Prophy-

laxis of recurrent otitis media and middle-ear

effusion. Am J Dis Child 143 1414, 1989

6. De Diego JI, Prim MP, Alfonso C, et al. Compari-

son of amoxicillin and azithromycin in the pre-

vention of recurrent acute otitis media. Int J

Pediatr Otorhinolaryngol 58 47, 2001

7. Herrod HG: management of the patient with IgG

subclass deficiency and/or selective antibody

deficiency. Ann Allergy 70 3, 1993

8. Philip Fireman. Primary Immunodeficiency

Disease. Atlas of Allergies and Clinical Immunol-

ogy 3rd edition Mosby Elsevier 348, 2006

9. Morimoto Y, Routes J. Immunodeficiency

Overview. Primary Care Clin Office Pract 35

159-73, 2008

10. Eijkhout HW, van den Briej PJ, vab der Nmeer

JW. Substitute therapy in immunodeficient pa-

tients with anti-IgA antibodies or severe adverse

reactions to previous immunoglobulin therapy.

Neth J Med 61(6) 213-7, 2003

11. Radinsky S, Bonagura VR. Subcutaneous immu-

noglobulin infusion as an alternative to intrave-

nous immunoglobulin. J Allergy Clin Immunol

112(3) 630-3, 2003

12. Diaz DH, Ortega JJ, Diaz MA et. Unrelated cord

blood transplantation for severe combined im-

m u n o d e f i c i e n c y a n d o t h e r p r i m a r y

immunodeficiencies. Bone Marrow Transplanta-

tion 41 627-33, 2008

13. C a n d o t t i F , R o i f m a n C , P u c k J M .

immunodeficiencies: injecting some safety into

SCID gene therapy? Gene therapy 13 741-3,

2006

14. Gennery AR, Cant AJ. Cord blood stem cell

transplantation in primary immune deficiencies.

Current Opinion in Allergy and Clinical Immu-

nology 7 528-34, 2007

(Submitted on 9/1/08)

Reference:

1. Bonilla FA, Stiehm ER, & Feldweg AM. Medical

therapy of immune deficiencywww.uptodate.com/

online/content/topic.do?topicKey=immunno/

5128&view=print 2008/5/2

2. Bruton OC. Agamglobulinemia. Pediatrics 9

722, 1952

3. Recommendations of the International Task Force

for Disease Eradication.MMWR Recomm Rep

42 1, 1993

4. Liston TE, Foshee WS, Pierson WD. Sulfisoxazole

chemoprophylaxis for frequent otitis media and


( ) -----

(Edward Jenner, 1749-1823)

(antibody)

B

B B (BCR)

(gene rearrangement) B

B B

B

(Class Switch) B M

(IgM) G(IgG) IgG IgM

(affinity) B IgG

B

IgG

B

(hypermutation)

IgG

IgG

IgG

IgG (Light Chain)

(Heavy Chain) (disulfide bond)

(variable region)

(constant region)

(antigen binding site)

(epitope) Fab IgG

2 CH2 CH3

(domain) Fc Fc

(complement)

C1q

(Natural Killer Cell NK cells)

(Macrophage) Fc

B

(polyclonal

antibody)

(monoclonal antibody)

1975 (Kohler) (Milstein)

B (myeloma cells)

(Hybridoma) B


(scleroderma)

( s y s temic sc l e roderma)

(localized scleroderma-morphea)

(diffuse cutaneous systemic scleroderma)

( l i m i t e d c u t a n e o u s s y s t e m i c

scleroderma)

1985 George Smith

(Phage display)

peptide

peptide

(genotype)

(Vector)

(Humanize)

Fc

Fc

2002 Ishida

KM

1. Charles A. Janeway, Jr. Immunology: the im-

mune system in health and disease 6th edition.

Garland Science Publishing New York, NY; 2004

2. Smith GP. Filamentous fusion phage: novel ex-

pression vectors that display cloned antigens on

the virion surface. Science New York, NY 228

(4705) 1315-7, 1985

3. Ishida I, Tomizuka K, Yoshida H, Tahara T,

Takahashi N, Ohguma A, Tanaka S, Umehashi M,

Maeda H, Nozaki C, Halk E and Lonberg N Pro-

duction of human monoclonal and polyclonal an-

tibodies in TransChromo (TC) animals. Cloning

Stem Cells 4(2002) 91-102


(generalized morphea) (plaque

morphea) (linear morphea)

(bullous morphea)

(deep morphea)

( ANA Scl 70

)

( MTX tacrolimus ) D-

penicillamine

(high dose UVA) D

ACE inhibitor

ACE inhibitor

(Anaphylaxis)

(Anaphylaxis)

( p r e v i o u s l y

sensitized)

E (IgE

antibody) (mast cell)

(basophil)

(histamine)

(Anaphylactoid reaction)

E

( N S A I D ) a s p i r i n

ibuprofen

0.4

Vol.9 No.3 September 2008 1111111111

(hyperventilation

syndrome) (anxiety attack)

(alcohol intoxication)

( )

( )

( )

( )

( )

(1)

( )

( )

(2)

( )

( )

( )

( )

(3)

( )

30%

( ) 90mmHg

30%

1.

2.

( 0.01

0.3 )

3.

4.

(

)

5.

(Desensitization)

(Immunotherapy)


CD4+ T

T (Th2 cell)

T

(cytokine)

GATA3 (zinc-finger)

T

GATA3 T

T

(transgenic mice)

GATA3

GATA3-positive

T

GATA3

GATA3

GATA3

T

GATA3 1.Antisense GATA3 treatment:

G A T A 3 a n t i s e n s e

phosphorthioate oligonucleotides T

GATA3 antisense

phosphorthioate oligonucleotides GATA3

T 2.Inhibition of

p38 function: GATA3 p38 mitogen-activated

protein kinase serine phosphorylated se-

lective p38 inhibitor p38

GATA3

T

GATA3

antisense oligonucleotides targeting p38

3 . R N A i ( S i R N A )

lentivirus-mediated GATA3 RNAi

GATA3 siRNA

lentivirus particle

T

GATA3

1. Sundrud MS, Grill SM, Ni D, Nagata K, Alkan

SS, Subramaniam A, et al.Genetic reprogramming

of primary human T cells reveals functional plas-

ticity in Th cell differentiation. J Immunol 171

3542-9, 2003

2. Lee GR, Flavell RA. Transgenic mice which over-

produce Th2 cytokines develop spontaneous

atopic dermatitis and asthma. Int Immunol 16

1155-60, 2004

3. Lee GR, Flavell RA. Transgenic mice which over-

produce Th2 cytokines develop spontaneous

atopic dermatitis and asthma. Int Immunol 16

1155-60, 2004

4. Nakamura Y, Christodoulopoulos P, Cameron L,

Wright E, Lavigne F, Toda M, et al. Upregulation

of the transcription factor GATA-3 in upper air-

way mucosa after in vivo and in vitro allergen

challenge. J Allergy Clin Immunol 105 1146-52,

2000

5. Nakamura Y, Ghaffar O, Olivenstein R, Taha RA,

Soussi-Gounni A, Zhang DH, et al. Gene expres-

sion of the GATA-3 transcription factor is in-

creased in atopic asthma. J Allergy Clin Immunol

103 215-22, 1999

6. Skapenko A, Leipe J, Niesner U, Devriendt K,

Beetz R, Radbruch A, et al. GATA-3 in human T

cell helper type 2 development. J Exp Med 199

Vol.9 No.3 September 2008 1515151515

expression. J Exp Med 193 1247-60, 2001

8. Cousins DJ, McDonald J, Lee TH. Therapeutic

approaches for control of transcription factors in

allergic disease .J Allergy Clin Immunol 121

803-9, 2008

(

)

( e x t e n s i v e l y

hydrolyzed) (partially hydrolyzed)

(amino acid-based formula)

(soy-based in-

fant formula)

(

)

(

)

423-8, 2004

7. Finotto S, De Sanctis GT, Lehr HA, Herz U,

Buerke M, Schipp M, et al. Treatment of allergic

airway inflammation and hyperresponsiveness by

antisenseinduced local blockade of GATA-3


(urticaria)

30%

(idiopathic urticaria)

- E (IgE-dependent)

IgE

( )

- IgE

-

-

vol.9 no.3 september, 2008air.org.tw/air/photo/過敏氣喘通訊vol.9 no.3.pdf · 2019-01-28 ·...

Documents