Interleukin 23和interleukin 23 receptor的免疫組織化學染色在移植腎臟的表現

Expression of interleukin 23 and interleukin 23 receptor in kidney transplant allografts

蕭匡智(Kuang-chih Hsiao)

指導教授 ： 張浤榮

中山醫學大學/醫學院/醫學研究所/碩士(2013年)

摘要

研究目的：移植病人的長期存活，始終是移植界所關注的主要問題。人體先天性和後天型免疫反應會把移植的腎臟認為是外來物質，產生細胞激素和發炎物質來攻擊移植腎臟。目前文獻發現T淋巴球製造的interleukin 23 (IL-23) 和interleukin 23 receptor (IL-23R)會造成移植腎臟排斥，可是在腎臟組織中IL-23和IL-23R的角色，時至今日仍無定論。故希望透過本研究，探討並分析在腎臟病理組織中，免疫組織化學染色法IL-23和IL-23R在移植腎臟切片上的表現。 研究方法及資料：回溯性分析自2009年7月1日至2011年8月31日，於中山醫學大學附設醫院腎臟科追蹤共31位腎臟移植患者住院接受腎臟切片檢查，將患者分成二組，一組病人腎功能惡化達到複合型指標的患者(composite outcome group)，即肌酸酐上昇兩倍或腎絲球過濾減少百分之三十，另一組病人則腎功能穩定未達複合型指標的病患(no composite outcome group)，在兩組病人腎臟病理組織使用免疫組織化學染色法IL-23和IL-23R，以斯皮爾曼等級相關係數探討臨床上各變數之關聯性和病理組織中免疫染色的差異性。 研究結果：腎移植患者接受腎臟切片檢查共有31 位，於追蹤期間腎功能惡化組有15 (48.3%)人，而腎功能穩定組共16 (51.7%)人。從數據中發現腎功能惡化組有較高的肌酸肝(p<0.001)、較差腎絲球過濾(p<0.001)和較低的白蛋白(p=0.025)。斯皮爾曼等級相關係數，在腎功能惡化組中，免疫染色IL-23R在萎縮的腎絲球間質細胞質有明顯負關連性(p=0.089)，但IL-23在腎臟各組織(腎絲球、腎小管、腎間質)並沒有統計差異。 結論與建議：移植腎功能惡化組病人在萎縮的腎絲球間質細胞的細胞質中有較低的IL-23R免疫染色強度。

關鍵字

腎臟移植 ； nterleukin 23 ； Interleukin 23 receptor

並列摘要

Background: Long-term survival of kidney transplant recipients remains an important issue. The allograft kidney was attacked by cytokines and inflammations produced by human immune system. Many studies revealed interleukin 23 (IL-23) and interleukin 23 receptor (IL-23R) play a role in the pathogenesis of allograft cellular and antibody rejection, but the histological association of IL-23/IL-23R and transplant kidney allograft is unclear. This study aimed to investigate the impact of expressions of immunohistochemistry IL-23 and IL-23R in kidney transplant allografts
Methods: Between July 2009 and August 2011, 31 renal transplant receipts who were admitted to receive sonography-guided allograft biopsy in a single center in central Taiwan were enrolled in this retrospective study. The patients were subdivided into two groups including composite outcome group with serum creatinine (Scr) doubling and lower estimated glomerular filtration rate (eGFR). The other one was defined as no composite outcome group. Specimens of 31 patients were examined by immunohistochemical stain of IL-23 and IL-23R in allograft kidneys, and the association of renal expression of IL-23/IL-23R and renal specimens were determined by spearmen’s collection test.
Results: Of the 31 patients, 15 patients (48.3%) were with the composite outcome group and the other 16 patients (52.7%) were without composite outcome group. Composite outcome group with double serum creatinine (SCr) had significantly higher SCr, lower eGFR, and low serum albumin (p=0.024). Univariate analysis showed the patients reaching the composite outcome were negatively associated with atrophic glomerular mesangial cell cytoplasmic IL-23R expression (p=0.089). IL-23 expression was not associated with the outcome in any of the renal tissue including glomerular, tubule and interstitium.
Conclusions: The patients of the composite outcome group had decreased expression of IL-23R in atrophic glomerular mesangial cell cytoplasm.

並列關鍵字

Renal transplantation ； Interleukin 23 ； Interleukin 23 receptor

參考文獻

Barnett, A. N., Hadjianastassiou, V. G., & Mamode, N. (2013). Rituximab in renal transplantation. Transpl Int, 26(6), 563-575.

Bour-Jordan, H., & Bluestone, J. A. (2009). Regulating the regulators: costimulatory signals control the homeostasis and function of regulatory T cells. Immunol Rev, 229(1), 41-66.

Braun, W. E. (2003). Renal transplantation: basic concepts and evolution of therapy. J Clin Apher, 18(3), 141-152.

Calne, R. Y., Thiru, S., McMaster, P., et al. (1998). Cyclosporin A in patients receiving renal allografts from cadaver donors. 1978. J Am Soc Nephrol, 9(9), 1751-1756.

Cendales, L. C., Kanitakis, J., Schneeberger, S., et al. (2008). The Banff 2007 working classification of skin-containing composite tissue allograft pathology. Am J Transplant, 8(7), 1396-1400.