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Vol.10 No.3 September 2009 1

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( ) - .............................. 9

....................................... 11

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A

1. 10 30 501

2. 11 15 9

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4. 11 8

5. 11 14

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Vol.10 No.3 September 200922222

50%

30% 10% 5%

5%

terpenes cinnamic acid caffeic acid

flavonoids

caffeic acid phenethyl ester(CAPE)

( )

caspase Akt

( )

CAPE

NF-kB

IKK IkBa

NF-kB DNA

DNA

T

Th1 Th2

( )

CAPE

CAPE NO

-

1 5 (Chizukit)

echinacea( ) C 3

2

TNF-a IL-6 IL-8 ICAM-1 LTD4 PGE2

IL-10

CAPE

References

1. HA Cohen, I Varsano, E Kahan, EM Sarrell, Y

Uziel: Effectiveness of an herbal preparation con-

taining echinacea, propolis, and vitamin C in pre-

venting respiratory tract infections in children: a

randomized, double-blind, placebo-controlled,

multicenter study. Arch Pediatr Adolesc Med

158 217-21, 2004

2. MT Khayyal, MA el-Ghazaly, AS el-Khatib, AM

Hatem, PJ de Vries, S el-Shafei, MM Khattab: A

clinical pharmacological study of the potential

beneficial effects of a propolis food product as an

adjuvant in asthmatic patients. Fundam Clin

Pharmacol 17 93-102, 2003

Vol.10 No.3 September 2009 33333

(juvenile rheuma-

toid arthritis or juvenile idiopathic arthritis)

JRA

JRA

(low peak aerobic capacity VO2peak)

Brussel

62 6-16 JRA VO2peak

1/4 JRA

JRA

Lelieveld

C H A Q - D I

(Childhood Health Assessment Questionnaire Dis-

ability Index)

23%JRA

66% JRA

(weight-bearing

exercise)

JRA

JRA

Net 45% JRA

70%

PEDI (Pediatric Evaluation of Disability

Inventory)

JRA

Takken

Singh-Grewal

CHAQ-DI

Epps

61% ACR 30

47%

6

JRA

(rest, ice, compression,

elevation, RICE)

Vol.10 No.3 September 200944444

1. Klepper SE. Exercise in pediatric rheumatic

diseases. Curr Opin Rheumatol 20 619-24,

2008

2. van Brussel M, Lelieveld OT, vander Net J, et al.

Aerobic and anaerobic capacity in children with

juvenile idiopathic arthritis. Arthritis Care Res

57 891-97, 2007

3. Lelieveld OT, van Brussel M, Takken T, et al.

Aerobic and anaerobic exercise capacity in ado-

lescents with juvenile idiopathic arthritis. Arthritis

Care Res 57 898-904, 2007

4. van der Net J, van der Torre P, Engelbert RH, et

al. Motor performance and functional ability in

preschool- and early school-aged children with

juvenile idiopathic arthritis: a cross-sectional

study. Pediatr Rheumatol Online J 6 2, 2008

Jan 16

5. Singh-Grewal D, Schneiderman-Walker J, Wright

V, et al. The effects of vigorous exercise training

on physical function in children with arthritis: a

randomized, controlled, single-blinded trail. Ar-

thritis Care Res 57 1202-10, 2007

6. Epps H, Ginnelly L, Utley M, et al. Is hydro-

therapy cost-effective? A randomized controlled

trial of combined hydrotherapy programmes com-

pared with physiotherapy land techniques in chil-

dren with juvenile idiopathic arthritis. Health

Technol Assess 9 1-59, 2005

( Curr Opin Rheumato 2008)

Vol.10 No.3 September 2009 55555

(steroid) (cyclosporin)

3

(an t i -RNP)

(Antinuclear antibody 1: 640)

Kasukawa et al 's

cr i ter ia

( e x . m e t h o t r e x a t e ,

cyclosporin, cyclophosphamide, azathioprine)

(transjugular intrahepatic portosystemic shunts,

TIPS) (Denver shunt)

(PPIs) sandostatin(Octreotide)

(gangrene)( )

(juvenile mixed connective tissue disease)

(

)

(tonsillar herniation)

(connective tissue disease)

(juvenile rheu-

matoid arthri t is , JRA)

Vol.10 No.3 September 200966666

(systemic lupus erythematosus, SLE)

(juvenile dermatomyositis)

(systemic sclerosis) overlaping

syndrome (mixed connec-

tive tissue disease, MCTD)

MCTD Sharp 1972

anti-RNP antibodies

Kasukawa 1987

MCTD

MCTD

0.1~0.3%

9 12 2 5.2

4 1

SLE

SLE

Raynaud's phenomenon

(9-57%)

R a y n a u d ' s

phenomenon

(gangrene)

temporo-parietal

Vol.10 No.3 September 2009 77777

MCTD

MCTD

MCTD

throm-

boxane A3 platelet-derived growth factor, connec-

tive tissue growth factor

2 MCTD

MCTD

( A N A ) ( a n t i -

RNP) (anti-RNP)

15 12

18

(vasculopathy) (extracellular

matrix abnormalities)

MCTD

(upper GI small bowel series)

(diffusing capacity of the lung for car-

bon monoxide)

D-penicillamine

MCTD

B T

1. James TC: Overlap syndromes. In: James TC,

Ross EP, eds. Textbook of pediatric rheumatology

5th edition. Saunders, Philadelphia

2. Michael LM MP: scleroderma and Raynaud

phenomenon. In: Robert MK, eds. Nelson Text-

book of pediatrics. 18th edition, Philadelphia,

Saunders,

3. Paul K. et al Treatment of Mixed Connective

Tissue Disease. Rheum Dis Clin N Am 31 549,

2005

4. Hoffman R. et al Immune pathogenesis of

Mixed Connective Tissue Disease: a short analyti-

cal review. Clin Immunol 128 8, 2008

5.

Vol.10 No.3 September 2009 99999

( ) --

B

B

B

B

(BCR) (gene rearrangement)

B (viability)

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)

(antigenic determinant or epitope)

Fab IgG 2

B

(noncovalent forces)

(electrostatic forces) (Hydrogen

bonds) (Van der Waals force)

(hydrophobic forces)

(specificity) (affinity)

C H 2 C H 3

(domain) Fc Fc

(compliment) C1q

(Natural Killer Cell, NK cells)

(Macrophage) Fc

Vol.10 No.3 September 20091010101010

a.

(RT-PCR)

(Q-PCR)

(f low

cytometer)

b.

c.

(enzyme- l inked

immunosorbent assay, ELISA)

(flowcytometry)

XX

+ XX + XX

1. Charles A. Janeway, Jr. Janeway's Immunobiology:

the immune system in health and disease 7th

edition. Garland Science Publishing New York,

NY; 2007

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 4 4 4 4 91-102, 2002

Vol.10 No.3 September 2009 1111111111

(mannose-binding lectin,

MBL) (mannose-binding

protein, MBP)

classic

pathway alternative pathway

( ) MBL

N-acety l -D-g lucosamine, mannose,

N-acetyl-mannosamine, fucose glucose

MBL

MBL-associated serine protease 2 (MASP-2)

C3 convertase1 MBL

(opsonophagocytosis) MBL

3

MBL C1q lectin (or car-

bohydrate-recognition) Domain (CRD) hydrophobic

neck region collagenous region cysteine-rich N-

terminal region 32kDa peptide

MBL( A)

MBL 10 (q21-24)2

MBL-2 gene exon 1 (single

nucleotide polymorphisms, SNPs)

codon 52(allele D) codon 54(allele B) codon

57(allele C)( B) MBL

promoter

M B L

(positions -550, -221 +4 H/L, X/Y, P/Q loci)

MBL 4

allele B (frequency 0.12-0.14)

Vol.10 No.3 September 20091212121212

(frequency 0.10-0.25) allele C

5 allele B

0.2 allele C allele

D

MBL

MBL MBL

MBL SNPs

MBL1,6

C3

MBL

leishmaniasis7

MBL MBL SNPs

MBL C8 MBL SNPs

9,10 MBL SNPs

MBL (RA)

MBL rheumatoid factor

MBL RA11,12

(JIA) 13 C1q

(SLE)

C1q MBL SLE

review MBL SLE 14,15

SLE MBL SLE5

MBL

MBL

MBL

MBL replacement therapy

References

1. Turner MW. The role of mannose-binding lectin

in health and disease. Mol Immunol 40 423-9,

2003

2. Tsutsumi A, Takahashi R, Sumida T. Mannose

binding lectin: genetics and autoimmune disease.

Autoimmun Rev 4 364-72, 2005

3. Jack DL, Read RC, Tenner AJ, Frosch M, Turner

MW, Klein NJ. Mannose-binding lectin regulates

the inflammatory response of human professional

phagocytes to Neisseria meningitidis serogroup B.

J Infect Dis 184 1152-62, 2001

4. Garred P, Larsen F, Seyfarth J, Fujita R, Madsen

HO. Mannose-binding lectin and its genetic

variants. Genes Immun 7 85-94, 2006

5. Tsai YC, Yao TC, Kuo ML, Cheng TT, Huang JL.

Lack of association of mannose-binding lectin

gene polymorphisms with development and clini-

cal manifestations of systemic lupus erythemato-

sus in chinese childhood. Lupus 18 372-6,

2008

6. Bouwman LH, Roep BO, Roos A. Mannose-bind-

ing lectin: clinical implications for infection,

transplantation, and autoimmunity. Hum

Immunol 67 247-56, 2006

7. Alonso DP, Ferreira AF, Ribolla PE, de Miranda

Santos IK, do Socorro Pires e Cruz M, de

Carvalho F, et al. Mannan-binding lectin en-

hances susceptibility to visceral leishmaniasis. J

Infect Dis 195 1212-7, 2007

8. Alves Pedroso ML, Boldt AB, Pereira-Ferrari L,

Steffensen R, Strauss E, Jensenius JC, et al.

Mannan-binding lectin MBL2 gene polymorphism

in chronic hepatitis C: association with the sever-

ity of liver fibrosis and response to interferon

therapy. Clin Exp Immunol 152 258-64, 2008

9. Koutsounaki E, Goulielmos GN, Koulentaki M,

Choulaki C, Kouroumalis E, Galanakis E. Man-

nose-binding lectin MBL2 gene polymorphisms

Vol.10 No.3 September 2009 1313131313

CD3-CD56+

10~15%

(MHC-unrestricted cytotoxicity)

C D 5 6

(~90%) CD56dim 10% CD56bright CD56dim

NK CD56bright

IFN-gamma,

TNF-alpha, GM-CSF, chemokines

iNKR(p58.1,p58.2, p70,

NKG2A, LIR-1) NCR(NKp30, NKp44, NKp46,

NKG2D) NK NK

N K ( i m m u n e

surveillance) NK

NK

1. -2(IL-2) IL-2

NK FDA

(metastatic renal cell carcinoma)

15~20% IL-2

2. -2(IL-2)

and outcome of hepatitis C virus-infected

patients. J Clin Immunol 28 495-500, 2008

10. Chong WP, To YF, Ip WK, Yuen MF, Poon TP,

Wong WH, et al. Mannose-binding lectin in

chronic hepatitis B virus infection. Hepatology

42 1037-45, 2005

11. Saevarsdottir S, Vikingsdottir T, Vikingsson A,

Manfredsdottir V, Geirsson AJ, Valdimarsson H.

Low mannose binding lectin predicts poor prog-

nosis in patients with early rheumatoid arthritis.

A prospective study. J Rheumatol 28 5728,

2001

12. Jacobsen S, Garred P, Madsen HO, Heegaard

NH, Hetland ML, Stengaard-Pedersen K, et al.

Mannose-binding lectin gene polymorphisms are

associated with disease activity and physical dis-

ability in untreated, anti-cyclic citrullinated

peptide-positive patients with early rheumatoid

arthritis. J Rheumatol 36 731-5, 2009

13. Gergely P Jr, B, Nagy ZB, Gombos T,

Rajczy K, Balogh Z, et al. Structural polymor-

phisms in the mannose-binding lectin gene are

associated with juvenile idiopathic arthritis. J

Rheumatol 36 843-7, 2009

14. Lee YH, Witte T, Momot T, Schmidt RE,

Kaufman KM, Harley JB, et al.: The mannose-

binding lectin gene polymorphisms and systemic

lupus erythematosus: two case-control studies

and a meta-analysis. Arthritis Rheum 52

3966-74, 2005

15. Monticielo OA, Mucenic T, Xavier RM, Brenol

JC, Chies JA. The role of mannose-binding lec-

tin in systemic lupus erythematosus. Clin

Rheumatol 27 413-9, 2008

Vol.10 No.3 September 20091414141414

IL-2 IL-15 IL-12 NK

(synergistic effect) IL-15 IL-2

IL-2br chain IL-15a IL-2

(reactive oxygen species, ROS)

IL-2 Vitamin. E

histamine ROS NK

GM-CSF IL-2

3. NK (adoptive transfer of NK cells)

GMP >90%

NK

(autologous NK cells) rhabdomycosareoma

AML multiple myeloma

malignant glioma

NK

NK

NK (allogeneic NK

cells)

allogeneic NK

KIR ligand mismatch, allogeneic NK

(GVHD)

KIR

(graft versus leukemia effect, GVL

effect)

4. NK (genetic manipulation)

electroporation, nucleofection

chimeric adenoviral retroviral vectors

(transduction) NK

( IL-15 gene)

NK

NK

NK (

)

NK

--

(Kawasaki Disease)

1967

15% (1)

(ESR) C-reactive protein

(CRP)(2)

( 10

6 6 - 6 9

) (3)

Vol.10 No.3 September 2009 1515151515

1~2

(New Ha-

ven )

53(4)

(5,6)

Lactobacillus

Casei (LCWE)

V

T (TCR)

(single nucleot ide

polymorphism, SNP)

Human Leukocyte Antigen

(HLA)-BW22 Tumor Necrosis Factor- -318A/G

Cytotoxic T lymphocyte antigen-4 (CTLA-4)

Mori

M.

HLA-A24, B25 DR2 (7)

HLA-E (rs2844724) (8)

T (ITPKC)(9)

(10)

(2 g/Kg)

Newburger

JW 2 g/Kg

-(11)

(TNF-a, interferon-gamma, interleukin-6..

)

(12) 20

Vol.10 No.3 September 20091616161616

(13)

7.8%~38%

10.8%

(14)

(15)

(Th2) (16)

(monocytosis)

(17) T

(1~2g/kg) 3-4%

cor t i cos tero id methy lpredni so lone pu l se

therapy cyclophosphamide cyclosporin tumor

n e c r o s i s f a c t o r - ( T N F - ) a n t a g o n i s t

methotrexate

(fistula) (18)

PS:

http://tw.myblog.yahoo.com/

erickuo48

1. Wang CL, Wu YT, Liu CA, Kuo HC, Yang KD.

Kawasaki disease: infection, immunity and

genetics. Pediatr Infect Dis J 24(11) 998-1004,

2005

2. Newburger JW, Takahashi M, Gerber MA, Gewitz

MH, Tani LY, Burns JC, et al. Diagnosis,

treatment, and long-term management of

Kawasaki disease: a statement for health profes-

sionals from the Committee on Rheumatic Fever,

Endocarditis and Kawasaki Disease, Council on

Cardiovascular Disease in the Young, American

Heart Association. Circulation 110(17) 2747-

71, 2004

3. Huang WC, Huang LM, Chang IS, Chang LY,

Chiang BL, Chen PJ, et al. Epidemiologic features

of Kawasaki disease in Taiwan, 2003-2006. Pedi-

atrics 123(3) e401-5, 2009

4. Chang LY, Chiang BL, Kao CL, Wu MH, Chen

PJ, Berkhout B, et al. Lack of association between

infection with a novel human coronavirus

(HCoV), HCoV-NH, and Kawasaki disease in

Taiwan. J Infect Dis 193(2) 283-6, 2006

5. Dominguez SR, Anderson MS, Glode MP,

Robinson CC, Holmes KV. Blinded case-control

study of the relationship between human

coronavirus NL63 and Kawasaki syndrome. J In-

fect Dis 194(12) 1697-701, 2006

6. Lehmann C, Klar R, Lindner J, Lindner P, Wolf

H, Gerling S. Kawasaki disease lacks association

with human coronavirus NL63 and human

Vol.10 No.3 September 2009 1717171717

bocavirus. Pediatr Infect Dis J 28(6) 553-4,

2009

7. Mori M, Miyamae T, Kurosawa R, Yokota S,

Onoki H. Two-generation Kawasaki disease:

mother and daughter. J Pediatr 139(5) 754-6,

2001

8. Lin YJ, Wan L, Wu JY, Sheu JJ, Lin CW, Lan YC,

et al. HLA-E gene polymorphism associated with

susceptibility to Kawasaki disease and formation

of coronary artery aneurysms. Arthritis Rheum

60(2) 604-10, 2009

9. Onouchi Y, Gunji T, Burns JC, Shimizu C,

Newburger JW, Yashiro M, et al. ITPKC func-

tional polymorphism associated with Kawasaki

disease susceptibility and formation of coronary

artery aneurysms. Nat Genet 40(1) 35-42, 2008

10. Burgner D, Davila S, Breunis WB, Ng SB, Li Y,

Bonnard C, et al. A genome-wide association

study identifies novel and functionally related

susceptibility Loci for Kawasaki disease. PLoS

Genet 5(1) e1000319, 2009

11. Uehara R, Belay ED, Maddox RA, Holman RC,

Nakamura Y, Yashiro M, et al. Analysis of poten-

tial risk factors associated with nonresponse to

initial intravenous immunoglobulin treatment

among Kawasaki disease patients in Japan.

Pediatr Infect Dis J 27(2) 155-60, 2008

12. van Bever HP, Quek SC, Lim T. Aspirin, Reye

syndrome, Kawasaki disease, and allergies; a

reconsideration of the links. Arch Dis Child

89(12) 1178, 2004

13. American Academy of Pediatrics. Influenza. In:

Pickering LK, ed. 2000 Red book: report of the

Committee on Infectious Diseases. 23rd ed. Elk

Grove Village, IL: American Academy of Pediat-

rics 2000 352-9.

14. Kuo HC, Yang KD, Liang CD, Bong CN, Yu HR,

Wang L, et al. The relationship of eosinophilia

to intravenous immunoglobulin treatment fail-

ure in Kawasaki disease. Pediatr Allergy

Immunol 18(4) 354-9, 2007

15. Kuo HC, Wang CL, Wang L, Yu HR, Yang KD.

Patient characteristics and intravenous immuno-

globulin product may affect eosinophils in

Kawasaki disease. Pediatr Allergy Immunol 19

(2) 184-5, 2008

16. Kuo HC, Wang CL, Liang CD, Yu HR, Huang

CF, Wang L, et al. Association of lower eosino-

phil-related T helper 2 (Th2) cytokines with

coronary artery lesions in Kawasaki disease.

Pediatr Allergy Immunol 20(3) 266-72, 2009

17. Kuo HC, Wang CL, Liang CD, Yu HR, Chen

HH, Wang L, et al. Persistent monocytosis after

intravenous immunoglobulin therapy correlated

with the development of coronary artery lesions

in patients with Kawasaki disease. J Microbiol

Immunol Infect 40(5) 395-400, 2007

18. Liang CD, Kuo HC, Yang KD, Wang CL, Ko SF.

Coronary artery fistula associated with Kawasaki

disease. Am Heart J 157(3) 584-8, 2009

Vol.10 No.3 September 20091818181818

-(component-resolved food allergy assay)

?

( )

( )

20-30%

3- 4%

6-8%

IgE IgE

( )

(urticaria) (angioedema)

(oral allergy syndrome)

(laryngospasm) (anaphylaxis)

(eosinophilic gastroenteritis)

( )

(

)

(skin prick

test) IgE ( MAST ImmunoCAP)

(food challenge test)

(component-resolved food allergy assay)

IgE

IgE

(cross reaction)

1990

Bet v 1 (

) Mal d 1

Vol.10 No.3 September 2009 1919191919

(lipid transfer proteins, LTP)

(skin prick test)

Ara h 1, Ara h 2 Ara h 3

Ara h 2

Ara h 2 IgE

(allergen microarray)

DNA

5000

(ant igenic determinant or

epitope) 3

1