The Clinical Significance of Soluble Intercellular Adhesion Molecule-1 sICAM-1) and Soluble Vascular Cell Adhesion Molecule-1(sVCAM-1) in Kawasaki Disease

급성 발열기 및 아급성기 가와사끼병에서 세포부착분자 sICAM-1, sVCAM-1의 임상적 의의

  • Rhee, Kang Won (Department of Pediatrics, College of Medicine, Chung-Ang University) ;
  • Yun, Sin Weon (Department of Pediatrics, College of Medicine, Chung-Ang University) ;
  • Lee, Dong Keun (Department of Pediatrics, College of Medicine, Chung-Ang University) ;
  • Choi, Eung Sang (Department of Pediatrics, College of Medicine, Chung-Ang University) ;
  • Yoo, Byeong Hoon (Department of Pediatrics, College of Medicine, Chung-Ang University) ;
  • Lee, Mi Kyung (Department of Laboratory Medicine, College of Medicine, Chung-Ang University)
  • 이강원 (중앙대학교 의과대학 소아과학교실) ;
  • 윤신원 (중앙대학교 의과대학 소아과학교실) ;
  • 이동근 (중앙대학교 의과대학 소아과학교실) ;
  • 최응상 (중앙대학교 의과대학 소아과학교실) ;
  • 유병훈 (중앙대학교 의과대학 소아과학교실) ;
  • 이미경 (중앙대학교 의과대학 진단검사의학교실)
  • Received : 2005.01.27
  • Accepted : 2005.03.09
  • Published : 2005.06.15

Abstract

Purpose : Kawasaki disease(KD) is known as an acute multi-systemic vasculitis with various immunologic abnormalities. Adhesion of leukocyte to endothelial cells is a key event in the sequence of inflammatory response. This study was performed to investigate the clinical significance of serum soluble intercellular adhesion molecule-1(sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in acute and subacute stages of typical KD for diagnostic and prognostic value. Methods : A typical KD group was 32 patients who were hospitalized from Jan. 2002 to Jun. 2004 was enrolled. Control was 16 non-KD patients with febrile illness. sICAM-1 and sVCAM-1 were measured and compared by Echocardiographic and clinical findings and cardiac troponin T and I. Results : sICAM-1 and sVCAM-1 levels of acute KD were significantly elevated over control(P=0.019 vs. P=0.049, respectively) and sICAM-1 was significantly decreased in subacute stage(P=0.0015). sICAM-1 and sVCAM-1 had positive correlation with each other in both stages(P=0.0067, P=0.015, retrospectively). Neither sICAM-1 nor sVCAM-1 correctly reflected the coronary abnormalities and responsiveness to intravenous gammaglobulin(IVGG) in both stages. But sVCAM-1 was significantly increased in the carditis group in both stages(P=0.025, P=0.014, retrospectively) and had a positive correlation with troponin T(r=0.63, P=0.00063). Conclusion : The levels of sICAM-1 and sVCAM-1 were not very useful tools for detecting and predicting subsequent coronary abnormalities and responsiveness to IVGG in KD patients. However, sVCAM-1 appears to play a significant role in carditis of KD. Further studies are needed about various adhesion molecules and cytokines in the pathogenesis of KD.

목 적 : 가와사끼병은 여러 가지 면역학적 이상을 보이는 혈관염으로 혈관 내피세포의 면역학적 기전과 관련하여 세포부착 분자가 관여하는 것으로 알려져 있다. 본 연구는 가와사끼병에서 세포부착분자 sICAM-1과 sVCAM-1을 급성 발열기와 아급성기로 나누어 비교 분석하였고 이들의 심장병변과 관련된 임상적 의의를 찾고자 하였다. 방 법 : 2002년 1월부터 2004년 6월까지 중앙대학교 의료원 소아과에 전형적인 가와사끼병으로 입원한 32명을 대상으로 감마글로불린 투여 전 급성 발열기와 발병 2주의 아급성기의 Troponin T와 I, 심장 초음파 검사 소견, sICAM-1, sVCAM-1을 비교, 분석하였고, 가와사끼병이 아닌 급성 발열성 질환으로 입원한 16명을 대조군으로 하였다. 결 과 : sICAM-1 및 sVCAM-1은 급성 발열기 가와사끼병에서 대조군에 비하여 의미있게 증가하고(P=0.019, P=0.049) 특히 sICAM-1은 급성발열기에 비하여 아급성기때 의미있게 감소하였다(P=0.0015). 급성 발열기, 아급성기 모두에서 sICAM-1과 sVCAM-1은 상호간에 양의 상관관계를 나타내었다(P=0.0067, P=0.015). sICAM-1, sVCAM-1 모두 정맥용 감마글로불린 투여 횟수 및 반응성 여부를 반영하지는 못하며, 관상동맥 병변의 정도를 의미있게 반영하지는 못하였으나, sVCAM-1의 경우 급성 발열기 및 아급성기 모두 심염군에서 통계적으로 의미있게 증가하였다(P=0.025, P=0.014). 또한 급성 발열기 sVCAM-1과 Troponin T는 양의 상관관계를 나타내었다(r=0.63, P=0.00063). 결 론 : sICAM-1과 sVCAM-1은 가와사끼병의 병인에 중요한 역할을 하나 감마글로불린 투여 횟수 및 반응성 여부를 반영하지는 못하며, 가장 중요한 합병증인 관상동맥병변을 직접적으로는 반영하지는 못한다. 그러나 sVCAM-1의 경우 심염에 있어 중요한 역할을 하는 것으로 여겨진다. 이에 대해서는 다양한 세포부착분자에 대하여 가와사끼병에서의 면역학적인 기전에 대한 추가 연구가 있어야 할 것으로 생각한다.

Keywords

References

  1. Kawasaki T. Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of fingers and toes. Arerugi 1967;16:178-222
  2. Hirose S, Hamashima Y. Morphological observations on the vasculitis in the mucocutaneous lymph node syndrome. Eur J Pediatr 1978;129:17-27 https://doi.org/10.1007/BF00441370
  3. Kato H, Ichinose E, Yoshioka F. Fate of coronary aneurysm in Kawasaki disease : serial coronary angiography and long-term follow-up study. Am J Cardiol 1982;49:1758-66 https://doi.org/10.1016/0002-9149(82)90256-9
  4. Leung DYM, Geha RS, Newburger JW, Burns JC, Fiers W, Lapierre LA, et al. Two monokines, interferon-1 and tumor necrosis factor, render cultured vascular endotherial cells susceptible to lysis by antibodies circulating during Kawasaki syndrome. J Exp Med 1986;164:1958-72 https://doi.org/10.1084/jem.164.6.1958
  5. Lin CY, Lin CC, Hwang B. Serial changes of IL-6, IL-8 and TNF-$\alpha$ among patients with Kawasaki disease. J Pediatr 1992;121:924-6 https://doi.org/10.1016/S0022-3476(05)80343-9
  6. Osborn L. Leukocyte adhesion to endothelium in inflammation.Cell 1990;62:3-6 https://doi.org/10.1016/0092-8674(90)90230-C
  7. Barnes PJ, Liew FY. Nitric oxide and asthma inflammation. Immunol Today 1995;16:128-30 https://doi.org/10.1016/0167-5699(95)80128-6
  8. Bereta J, Bereta M, Allison AC, Kruger PB, Koj A. Inhibitory effect of di-catechol rooperol on VCAM-1 and iNOS expression in cytokine-stimulated endothelium. Life Sci 1997;60:325-34
  9. Kim SK. Inflammatory markers in coronary artery disease. Korean Circ J 2001;31:617-9
  10. Shimizu Y, Newman W, Shaw S. Lymphocyte interactions with endothelial cells. Immunol Today 1992;13:106-12 https://doi.org/10.1016/0167-5699(92)90151-V
  11. Zimerman GA, Prescott SM, McIntyre TM. Endotherial cell interactions with granulocytes : tethering and signaling molecules. Immunol Today 1992;13:93-100 https://doi.org/10.1016/0167-5699(92)90149-2
  12. Gearing AJH, Newman W. Circulating adhesion molecules in disease. Immunol Today 1993;14:506-12 https://doi.org/10.1016/0167-5699(93)90267-O
  13. Takeshita S, Dobashi H, Nakatani K, Koike Y, Tsujimoto H, Hirayama K, et al. Circulating soluble selectins in Kawasaki disease. Clin Exp Immunol 1997;108:446-50 https://doi.org/10.1046/j.1365-2249.1997.3852128.x
  14. Americian Heart Association. Diagnostic guidelines for Kawasaki disease. Circulation 2001;87:1776-80
  15. Kurotobi S, Nagai T, Kawakami N, Sano T. Coronary diameter in normal infants, children and patients with Kawasaki disease. Pediatr Int 2002;44:1-4 https://doi.org/10.1046/j.1442-200X.2002.01508.x
  16. Burns JC, Kushner HI, Bastian JF, Shike H, Shimizu C, Matubara T, et al. Kawasaki disease : A brief history. Pediatrics 2000;106:e27 https://doi.org/10.1542/peds.106.1.27
  17. Park CS, Suh CJ, Cho SH, Lee DB. Muco-cutaneous lymphnode syndrome : five cases report. J Korean Pediatr Soc 1973;16:61-7
  18. Park YW, Park IS, Kim CH, Ma JS, Lee SB, Kim CH, et al. Epidemiologic study of Kawasaki disease in Korea, 1997-1999 : Comparison with previous studies during 1991-1996. J Korean Med Sci 2002;17:453-6
  19. Jang YJ, Kim JG, Yun YS. The clinical observation in Kawasaki disease. J Korean Med Sci 1992;35:330-41
  20. Levein M, Tizard EJ, Dillon MJ. Kawasaki disease : recent advanced. Arch Dis Child 1991;66:1369-72 https://doi.org/10.1136/adc.66.12.1369
  21. Curtis N, Levin M. Superantigen disease. Res Adv Pross 1996;15:31-51
  22. Leung DYM, Meissner C, Fluton D, Schlievert PM. The potential role of bacterial superantigens in the pathogenesis of Kawasaki syndrome. J Clin Immunol 1995;15:11-7 https://doi.org/10.1007/BF01540888
  23. Leung DYM. Superantigens related to Kawasaki syndrome. Springer Semin Immunopathol 1996;17:385-96
  24. Rowley AH, Shulman ST. Kawasaki syndrome. Pediatr Clin North Am 1999;46:313-29 https://doi.org/10.1016/S0031-3955(05)70120-6
  25. Maury CP, Salo E, Pelkonen P. Circulating interleukin-1 beta in patients with Kawasaki disease. N Engl J Med 1988;319:1670-1 https://doi.org/10.1056/NEJM198812223192515
  26. Lasky LA. Selectins : Interpreters of cell-specific carbohydrate information during inflammation. Science 1992;258:964-9 https://doi.org/10.1126/science.1439808
  27. Williams AF, Barclay AN. The immunoglobulin superfamily-domains for cell surface recognition. Annu Rev Immunol 1988;6:381-405 https://doi.org/10.1146/annurev.iy.06.040188.002121
  28. Alzari PM, Lascombe MB, Poljak RJ. Three-dimensional structure of antibodies. Annu Rev Immunol 1988;6:555-80 https://doi.org/10.1146/annurev.iy.06.040188.003011
  29. Faruqi RM, DiCorleto PE. Mechanisms of monocyte recruitment and accumulation. Br Heart J 1993;69(1 Suppl):19S-29S https://doi.org/10.1136/hrt.69.1_Suppl.S19
  30. Ross R. Atherosclerosis - an inflammatory disease. N Engl J Med 1999;340:115-26 https://doi.org/10.1056/NEJM199901143400207
  31. Rader DJ. Inflammatory markers of coronary risk. N Engl J Med 2000;343:1179-82 https://doi.org/10.1056/NEJM200010193431609
  32. Yun SW. Diagnostic value of serum cardiac troponin T, troponin I and CK-MB in acute Kawasaki disease. Korean Circ J 2004;34:82-92
  33. Yanagawa H, Nakamura Y, Yashiro M, Ojima T, Koyanagi H, Kawasaki T. Update of the epidemiology of Kawasaki disease in Japan - from the results of 1993-94 nationwide survey. J Epidemiol 1996;6:148-57 https://doi.org/10.2188/jea.6.148
  34. Park YW, Park IS, Kim CH, Ma JS, Lee SB, Kim CH, et al. Update of an epidemiologic study of Kawasaki disease in Korea, comparing with the results of 1991-96 survey. Program and Abstract, the 51st Annual Fall Meeting of the Korean Pediatric Society; 2001 Oct 19-20; Seoul. Seoul :The Korean Pediatric Society, 2001:83
  35. Lee KY, Park MY, Han JW, Lee HS, Choi J, Whang KT. An epidemiologic study of Kawasaki disease(1987-2000) :Incidence of coronary artery complication in the acute stage. J Korean Pediatr Soc 2002;45:783-9
  36. Harada K. Intravenous $\gamma$-globulin treatment in Kawasaki disease. Acta Pediatr Jpn 1991;33:805-10 https://doi.org/10.1111/j.1442-200X.1991.tb02612.x
  37. Hamamichi Y, Ichida F, Yu X, Hirono KI, Uese KI, Hashimito I, et al. Neutrophils and mononuclear cells express vascular endothelial growth factor in acute Kawasaki disease : its possible role in progression of coronary artery lesions. Pediatr Res 2001;49:74-80 https://doi.org/10.1203/00006450-200101000-00017