The effects of high-dose intravenous immunoglobulin on plasma protein and lipid levels in the patients with Kawasaki disease

가와사끼병에서 고용량 정맥용 면역글로불린이 혈장 단백 및 지질에 미치는 영향(면역글로불린 투여 후 단백질 농도 변화)

  • Lee, Keun Young (Department of Pediatrics, College of Medicine, The Catholic University of Korea) ;
  • Kim, Dong-Un (Department of Pediatrics, College of Medicine, The Catholic University of Korea) ;
  • Lee, Hyun Seung (Department of Pediatrics, College of Medicine, The Catholic University of Korea) ;
  • Jang, Pil Sang (Department of Pediatrics, College of Medicine, The Catholic University of Korea) ;
  • Kim, Young-Hoon (Department of Pediatrics, College of Medicine, The Catholic University of Korea) ;
  • Kim, Jin Tack (Department of Pediatrics, College of Medicine, The Catholic University of Korea) ;
  • Kim, Hyun Hee (Department of Pediatrics, College of Medicine, The Catholic University of Korea) ;
  • Lee, Kyung-Yil (Department of Pediatrics, College of Medicine, The Catholic University of Korea) ;
  • Lee, Joon-Sung (Department of Pediatrics, College of Medicine, The Catholic University of Korea)
  • 이근영 (가톨릭대학교 의과대학 소아과학교실) ;
  • 김동언 (가톨릭대학교 의과대학 소아과학교실) ;
  • 이현승 (가톨릭대학교 의과대학 소아과학교실) ;
  • 장필상 (가톨릭대학교 의과대학 소아과학교실) ;
  • 김영훈 (가톨릭대학교 의과대학 소아과학교실) ;
  • 김진택 (가톨릭대학교 의과대학 소아과학교실) ;
  • 김현희 (가톨릭대학교 의과대학 소아과학교실) ;
  • 이경일 (가톨릭대학교 의과대학 소아과학교실) ;
  • 이준성 (가톨릭대학교 의과대학 소아과학교실)
  • Received : 2006.07.14
  • Accepted : 2006.09.13
  • Published : 2006.12.15

Abstract

Purpose : The reticuloendothelial system is composed of sinusoidal capillaries, through which even large protein molecules are freely movable between plasma and interstitial space, including the lymphatic system. Therefore, high-dose intravenous immunoglobulin (IVIG) would cause a redistribution of proteins between two compartments. To investigate this hypothesis, we measured plasma protein and lipid levels in patients with Kawasaki disease before and after high-dose IVIG treatment. Methods : Thirty four children with Kawasaki disease who had complete responses to high-dose IVIG treatment (1 g/kg/day for two consecutive days), were analyzed. Before and after the administration of IVIG, serum analyses were performed for such parameters as total protein, albumin, ${\gamma}$-globulins (IgG, IgM, IgA), ${\alpha}1-$, ${\alpha}2-$, and ${\beta}-$ globulin fractions, and lipid profiles (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglyceride). Results : The levels of ${\gamma}$-globulins including IgG, IgM, IgA were significantly increased, and IgG was increased by $1,779{\pm}304mg/dL$ after two-dose of IVIG infusion. The levels of albumin, ${\alpha}1-$, ${\alpha}2-$, and ${\beta}$ globulin fractions were significantly decreased by 18 percent, 24 percent, 19 percent and 12 percent, respectively. HDL-cholesterol level was significantly decreased by 20 percent, while LDL-cholesterol and triglyceride levels were significantly increased by 21 percent and 50 percent, respectively. The total cholesterol level was not changed. Conclusion : High-dose IVIG treatment decreased the levels of a variety of proteins except immunoglobulins, and the increase of IgG after IVIG treatment was lower than expected. Our results suggest that a part of infused IVIG and plasma proteins, including etiologic proteins for Kawasaki disease, may be distributed to the extravascular compartments. The rapid improvement of symptoms induced by IVIG in Kawasaki disease might be explained by this mode of action of IVIG.

목 적 : 고용량의 IVIG의 투여가 어떠한 기전으로 가와사끼병 환자들의 임상증상을 급속히 호전시키는지는 아직도 확실히 밝혀진 것은 없으나 항원-항체 반응에 의한 원인 항원의 제거도 한 가지 유력한 학설이다. 간이나 비장의 세망내피계는 굴형 모세혈관으로 이루어져 있어서 분자량이 큰 단백질들도 혈장과 간질 사이의 상호 이동이 가능하다. 본 연구자들은 대량의 IVIG 투여 후에 투여된 IgG 및 기타 단백질들의 혈장과 간질 사이의 재분포가 있을 가능성을 가정하고 IVIG 2 g/kg 투여 전후의 혈장 단백질 및 지질 농도를 측정하여 어떠한 변화가 일어나는지 알아보았다. 방 법 : 2004년 3월부터 2006년 2월까지 의정부 성모병원에 가와사끼병으로 입원하여 IVIG 1 g/kg를 2일 연속 두 차례에 걸쳐 총 2 g/kg를 투여 받은 34명을 대상으로 하였다. IVIG가 투여 전과 투여가 종료된 다음날(12-18시간 후) 두 차례 혈액을 채취하여, 총단백, 알부민, IgG, IgM, IgA, CRP, 그리고 혈청전기영동상의 ${\alpha}1$ 글로불린, ${\alpha}2$ 글로불린, ${\beta}$ 글로불린 및 혈청지질(총콜레스테롤, HDL-콜레스테롤, LDL-콜레스테롤, 중성지방)의 변화를 살펴보았다. 결 과 : IVIG 투여 후에 혈청 IgG, IgM, IgA 등 ${\gamma}$ 글로불린은 유의하게 상승하였고, IgG의 상승량은 $1,779{\pm}304mg/dL$이었다. 한편, 알부민, ${\alpha}1$ 글로불린, ${\alpha}2$ 글로불린 및 ${\beta}$ 글로불린은 각각 18%, 24%, 19% 및 12%의 유의한 감소를 보였다. 혈청 지질치는 HDL-콜레스테롤은 유의하게 감소한 반면(20%), LDL-콜레스테롤과 중성지방은 각각 21%와 50%의 유의한 증가를 보였다. 결 론 : IVIG 투여 후 ${\gamma}$ 글로불린을 제외한 대부분의 단백질들이 감소하며, IgG의 상승도 예상 혈청 IgG 농도에 미치지 못하였다. 이러한 결과들은 투여된 IVIG에 의해 IgG의 일부와 가와사끼병에서 임상 증상을 일으키는 원인 단백을 포함한 단백들이 혈관 밖 구역으로의 이동 가능성을 제시한다.

Keywords

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