IgA 신병증에서 15-Deoxy-Delta(12,14)-Prostaglandin J2 및 염증성 사이토카인의 역할 = 15-Deoxy-Delta(12,14)-Prostaglandin J2 andProinflammatory Cytokines in IgA Nephropathy

다국어 초록 (Multilingual Abstract)

Purpose : This study was performed to demonstrate a correlation among urinary 15d-PGJ2, proinflammatory cytokines (i.e. IL-23, IL-6, and TGF-β1), and CRP, and to determinate the contributors to prognostic score and proteinuria in IgAN patients.
Methods : Fifty-four patients with biopsy-proven IgAN were enrolled. For comparison with IgAN, five MCD patients were also enrolled. Immunohistochemical staining for PPAR-γ in kidney tissue and measurements of urinary IL-6, IL-23, TGF-β1, 15d-PGJ2 and serum CRP were performed
Results : There was no difference according to PPAR-γ staining. 15d-PGJ2 was negatively correlated with urinary IL-23, TGF-β1, and CRP. Among proinflammatory cytokines and CRP, there were positive relationships with each other except for IL-23 and CRP. TGF-β1 in the group having proteinuria more than 3 g/day was statistically higher than that in the sole hematuria group. However, in multivariate regression analysis, not a single relation was found between TGF-β1 and proteinuria. Prognostic score was correlated with IL-6, IL-23, TGF-β1, CRP, 15d-PGJ2, and 24hr proteinuria. 24hr proteinuria was correlated with IL-6 and 15d-PGJ2. In multivariate regression analysis, CRP, 15d-PGJ2, and 24hr proteinuria contributed to prognostic score, and only 15d-PGJ2 contributed to 24hr proteinuria. Last, urinary 15d-PGJ2 in IgAN was higher than that in MCD.
Conclusion : Endogenous 15d-PGJ2 was associated with inflammation and might be considered as a material which could delay the damage of kidney in IgAN. In the future, larger cohort and long-term follow-up studies are needed to demonstrate the role of 15d-PGJ2 as prognostic indicator or marker of kidney damage.

국문 초록 (Abstract)

목 적 : 15-deoxy-delta(12,14)-prostaglandin J2 (15d- PGJ2)은 prostaglandin D2 대사로부터 생성되며 PPAR-γ의 내인성 ligand로 알려져 있다. 또한, 여러 연구에서 15d- PGJ2의 항염증 효과에 대해 보고하고 있다. 최근 다양한 원인에 의한 신손상에 복잡한 염증작용이 관여하고 있으며 이에 대한 연구가 증가하고 있는 추세이다. 본 연구에서는 IgA 신병증에서 15d-PGJ2가 염증 조절자로서 역할을 할 것으로 가정하고 다른 염증성 사이토카인과 비교 연구함으로써 그 역할을 구명하고자 하였다. 또한 최근 제안된 IgA 신병증에서의 예후점수와 단백뇨간의 상관관계 분석 및 미세변화신증과의 비교를 해보고자 하였다.
방 법 : 신조직 검사로 확진된 54명의 IgA 신병증 환자와 5명의 미세변화신증 환자를 대상으로 하였다. 신조직에 대해 PPAR-γ 단클론 항체를 이용하여 면역조직화학 염색을 시행하였고 신조직 당일에 CRP를 포함한 혈청 검사와 수집된 검체를 이용하여 요중 IL-6, IL-23, TGF-β1, 15d-PGJ2를 측정하였다.
결 과 : 신조직의 PPAR-γ 양성군과 음성군간에 염증성 사이토카인과 CRP, 15d-PGJ2의 차이는 없었다. 15d-PGJ2와 염증성 사이토카인 및 CRP와의 상관관계에서는 15d- PGJ2가 IL-23 (r=-0.293 p=0.031), TGF-β1 (r=-0.427, p<0.001), CRP (r=-0.444, p<0.001)와 음의 상관관계가 있었으며 CRP와 염증성 사이토카인 사이에는 IL-23와 CRP사이를 제외하고는 모두에서 양의 상관관계가 있었다. 신증후군 수준의 단백뇨를 보이는 IgA 신병증군에서 단백뇨가 없는 군에 비해 요중 TGF-β1 배설이 많았으나 다중회귀분석에서는 TGF-β1와 단백뇨 사이의 관련성은 없었다. 염증성 사이토카인과 CRP는 예후점수와 양의 상관관계가 있었으며 15d-PGJ2는 예후점수와 음의 상관관계가 있었다. 다중회귀분석에서 CRP와 15d-PGJ2, 24시간 단백뇨가 예후점수에 영향을 주었으며 24시간 단백뇨에 영향을 주는 인자는 15d- PGJ2 뿐이었다. 미세변화신증과의 비교에서는 염증성 사이토카인 및 CRP는 양군에서 차이가 없었으며 15d-PGJ2가 IgA 신병증에서 미세변화신증에 비해 높았다.
결 론 : 내인성 15d-PGJ2는 IgA 신병증에서 염증작용과 관련이 있었으며 예후점수와 단백뇨와의 관련성에 근거하여 신손상을 줄여 줄 수 있는 인자로서 고려해 볼 수 있겠다. 향후 더 많은 환자의 추적 관찰을 통해 15d-PGJ2의 역할에 대한 연구가 필요할 것으로 판단한다.

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