Brenchley Paul E, Poulton Kay, Morton Muir, Picton Michael L
Manchester Institute of Nephrology and Transplantation, Central Manchester University Hospital NHS Trust, Oxford Road, Manchester M13 9WL, UK.
Manchester Institute of Nephrology and Transplantation, Central Manchester University Hospital NHS Trust, Oxford Road, Manchester M13 9WL, UK.
Transplant Rev (Orlando). 2014 Jul;28(3):140-4. doi: 10.1016/j.trre.2014.01.004. Epub 2014 Jan 27.
Glomerulonephritis is a significant cause of chronic kidney disease requiring renal replacement therapy. For patients receiving a transplant, it is known that specific primary pathologies such as membranous nephropathy, IgA nephropathy and FSGS have a high risk of recurrence in the transplant but the reasons for this are unknown and the ability to predict recurrence is poor. The recent discovery that primary MN is an autoimmune disease characterised by an autoantibody to phospholipase A2 receptor 1 and the identification of two genes, PLA2R1 and DQA1 which account for the genetic susceptibility to the disease, open up the potential to understand the mechanism of recurrent MN and therefore to design and manage therapy to prevent recurrence. Transplantation offers a unique ethical experimental context in which to explore the genetic contribution to recurrent autoimmune membranous nephropathy. By analysing the genetic changes in the kidney transplant in the context of anti-PLA2R status post transplant, it may be possible to link genetic markers, anti-PLAR regulation with recurrence and non-recurrence of disease. If successful, similar strategies may help unravel mechanisms of recurrent IgA nephropathy and FSGS.
肾小球肾炎是需要肾脏替代治疗的慢性肾脏病的重要病因。对于接受移植的患者，已知某些特定的原发性病理类型，如膜性肾病、IgA肾病和局灶节段性肾小球硬化症，在移植肾中有较高的复发风险，但原因不明且预测复发的能力较差。最近发现原发性膜性肾病是一种自身免疫性疾病，其特征是存在针对磷脂酶A2受体1的自身抗体，并且鉴定出两个与该疾病遗传易感性相关的基因PLA2R1和DQA1，这为理解复发性膜性肾病的发病机制以及设计和管理预防复发的治疗方法开辟了可能性。移植提供了一个独特的伦理实验环境，可用于探索遗传因素对复发性自身免疫性膜性肾病的影响。通过分析移植后抗PLA2R状态下肾移植中的基因变化，有可能将遗传标记、抗PLA2R调节与疾病的复发和不复发联系起来。如果成功，类似的策略可能有助于揭示复发性IgA肾病和局灶节段性肾小球硬化症的发病机制。
